treatments-xml/data/03/FB/87/03FB8795FF82BD495E50B9D7E2201FC8.xml

<document id="6379581AD2F3A2AB24DA6E24B4925AE4" ID-DOI="10.1016/j.phytochem.2021.112909" ID-ISSN="1873-3700" ID-Zenodo-Dep="8258118" IM.bibliography_approvedBy="juliana" IM.illustrations_approvedBy="juliana" IM.materialsCitations_approvedBy="felipe" IM.metadata_approvedBy="felipe" IM.tables_approvedBy="juliana" IM.taxonomicNames_approvedBy="juliana" IM.treatments_approvedBy="juliana" checkinTime="1692305013203" checkinUser="felipe" docAuthor="Chakraborty, Kajal &amp; Dhara, Shubhajit" docDate="2021" docId="03FB8795FF82BD495E50B9D7E2201FC8" docLanguage="en" docName="Phytochemistry.191.112909.pdf" docOrigin="Phytochemistry (112909) 191" docSource="http://dx.doi.org/10.1016/j.phytochem.2021.112909" docStyle="DocumentStyle:F36D69FC8B198FBE91029DF9C24697D3.5:Phytochemistry.2020-.journal_article" docStyleId="F36D69FC8B198FBE91029DF9C24697D3" docStyleName="Phytochemistry.2020-.journal_article" docStyleVersion="5" docTitle="Turbinaria conoides Kutzing" docType="treatment" docVersion="1" lastPageNumber="8" masterDocId="FFC2FFEDFF87BD4E5D62BD00E6061D71" masterDocTitle="Conoidecyclics A-C from marine macroalga Turbinaria conoides: Newly described natural macrolides with prospective bioactive properties" masterLastPageNumber="14" masterPageNumber="1" pageNumber="6" updateTime="1692621155424" updateUser="juliana">
<mods:mods id="94D4F88830048115C4B8ADC830A384F8" xmlns:mods="http://www.loc.gov/mods/v3">
<mods:titleInfo id="FD97A2F51F07A6BECC27F4D3E5B06E51">
<mods:title id="349978E945BFF7771433D2CD2BE9B4B8">Conoidecyclics A-C from marine macroalga Turbinaria conoides: Newly described natural macrolides with prospective bioactive properties</mods:title>
</mods:titleInfo>
<mods:name id="1F7D990CF09BC7E67E8086ABC125A59E" type="personal">
<mods:role id="561056A2B2A1DF46A8E4D6D8E9D1CE0B">
<mods:roleTerm id="4124C72D2B90AA43A37232928A01EB2D">Author</mods:roleTerm>
</mods:role>
<mods:namePart id="0BC18ABF9991BBC8CA7C0EAE287FD85B">Chakraborty, Kajal</mods:namePart>
<mods:affiliation id="F1E5FF5641F84E1A90CD28C5DD93B885">* &amp; Marine Bioprospecting Section of Marine Biotechnology Division, Central Marine Fisheries Research Institute, Ernakulam North, P. B. No. 1603, Cochin, Kerala State, &amp; *</mods:affiliation>
</mods:name>
<mods:name id="EC3C0EC2EADEA7CE7EB30EEA01519E4C" type="personal">
<mods:role id="748E6DE55592617BEAA9255247936335">
<mods:roleTerm id="22D0734DE81A8A41F8B76699DA0E33BF">Author</mods:roleTerm>
</mods:role>
<mods:namePart id="2F02A27E7A5A92883DD24691EB139343">Dhara, Shubhajit</mods:namePart>
</mods:name>
<mods:typeOfResource id="785CA872898FB577FCDB72C22DEB3FEA">text</mods:typeOfResource>
<mods:relatedItem id="8E6ACD15EB2E532052FCA7079BE46C29" type="host">
<mods:titleInfo id="5D18CCC7765F4E5ED18B6FECEF7E387D">
<mods:title id="88DBA43A01A10AD0F3B57FC449513568">Phytochemistry</mods:title>
</mods:titleInfo>
<mods:part id="3C631823804A188196872E90848FFAE2">
<mods:date id="258EA99401F2F4211A28D831DB498FB6">2021</mods:date>
<mods:detail id="A3963710D40B83DB1B5C0F849CD07092" type="series">
<mods:title id="B492C18A0C1C2235C4930855E2E283B3">112909</mods:title>
</mods:detail>
<mods:detail id="04DFABF84F6C197F8E282D5764762B76" type="pubDate">
<mods:number id="9F045329C31C6BBBE5909289BF4FF73B">2021-11-30</mods:number>
</mods:detail>
<mods:detail id="1F1A0AFDADEFA4159B9DD7A6D3BC2762" type="volume">
<mods:number id="F8D3653A7B4838372A1819A61826564C">191</mods:number>
</mods:detail>
<mods:extent id="53B1258F7D1DB12CD94AC55B1C431DA6" unit="page">
<mods:start id="3CFB6D8D00DB6C978E4D78A6CE1F7C7A">1</mods:start>
<mods:end id="73807AA80985485E9326A2EC755817AC">14</mods:end>
</mods:extent>
</mods:part>
</mods:relatedItem>
<mods:location id="DD4CC7754795F42AFA0C40B2C3272BFE">
<mods:url id="CBBD80CCB54DF54A5563E187C8252DAF">http://dx.doi.org/10.1016/j.phytochem.2021.112909</mods:url>
</mods:location>
<mods:classification id="8EB7067D948FA2DD5E3E22AE1AE09F55">journal article</mods:classification>
<mods:identifier id="7BE19EB26975815CCB80EC2FFCB79E86" type="DOI">10.1016/j.phytochem.2021.112909</mods:identifier>
<mods:identifier id="7B189A4AF3266DD40BEB0932D4800272" type="ISSN">1873-3700</mods:identifier>
<mods:identifier id="5D9AE7A312B8FA77CDA527D8E8FAAD80" type="Zenodo-Dep">8258118</mods:identifier>
</mods:mods>
<treatment id="03FB8795FF82BD495E50B9D7E2201FC8" LSID="urn:lsid:plazi:treatment:03FB8795FF82BD495E50B9D7E2201FC8" httpUri="http://treatment.plazi.org/id/03FB8795FF82BD495E50B9D7E2201FC8" lastPageId="7" lastPageNumber="8" pageId="5" pageNumber="6">
<subSubSection id="C3486508FF82BD4B5E50B9D7E3A91998" box="[818,1455,1238,1258]" pageId="5" pageNumber="6" type="nomenclature">
<paragraph id="8BED3683FF82BD4B5E50B9D7E3A91998" blockId="5.[818,1455,1238,1258]" box="[818,1455,1238,1258]" pageId="5" pageNumber="6">
<heading id="D0A581EFFF82BD4B5E50B9D7E3A91998" bold="true" box="[818,1455,1238,1258]" fontSize="36" level="1" pageId="5" pageNumber="6" reason="1">
<emphasis id="B926EA91FF82BD4B5E50B9D7E3A91998" bold="true" box="[818,1455,1238,1258]" italics="true" pageId="5" pageNumber="6">
2.4. Bioactive potential of the conoidecyclics isolated from 
<taxonomicName id="4C524D00FF82BD4B582BB9D7E3A91998" authority="(J. Agardh) Kutzing" authorityName="Kutzing" baseAuthorityName="J. Agardh" box="[1353,1455,1238,1258]" class="Anthozoa" family="Dendrophylliidae" genus="Turbinaria" kingdom="Animalia" order="Scleractinia" pageId="5" pageNumber="6" phylum="Cnidaria" rank="species" species="conoides">T. conoides</taxonomicName>
</emphasis>
</heading>
</paragraph>
</subSubSection>
<subSubSection id="C3486508FF82BD495E33B80FE2201FC8" lastPageId="7" lastPageNumber="8" pageId="5" pageNumber="6" type="description">
<paragraph id="8BED3683FF82BD4B5E33B80FE36C1A21" blockId="5.[818,1488,1295,1873]" pageId="5" pageNumber="6">
Conoidecyclic A exhibited dual attenuation property against inducible inflammatory enzymes COX-2 and 5-LOX (IC 
<subScript id="17D634C6FF82BD4B5860B831E312184E" attach="left" box="[1282,1300,1329,1343]" fontSize="6" pageId="5" pageNumber="6">50</subScript>
1.75 and 4.24 mM, respectively). The anti-inflammatory activities of conoidecyclic A were higher than those displayed by conoidecyclic B (IC 
<subScript id="17D634C6FF82BD4B587CB869E3361806" attach="left" box="[1310,1328,1385,1399]" fontSize="6" pageId="5" pageNumber="6">50</subScript>
<emphasis id="B926EA91FF82BD4B585AB862E34E1804" box="[1336,1352,1378,1397]" italics="true" pageId="5" pageNumber="6">&gt;</emphasis>
1.9 mM) and conoidecyclic C (IC 
<subScript id="17D634C6FF82BD4B5E8AB885E22B18E2" attach="left" box="[1000,1069,1413,1427]" fontSize="6" pageId="5" pageNumber="6">50 5-LOX</subScript>
5.07 mM) (
<tableCitation id="C6D00338FF82BD4B59FDB87EE2E318E0" box="[1183,1253,1406,1425]" captionStart="Table 2" captionStartId="6.[100,150,150,166]" captionTargetPageId="6" captionText="Table 2 Bioactivities of conoidecyclics A-C isolated from the organic extract of T. conoides and their molecular descriptors." pageId="5" pageNumber="6">Table 2</tableCitation>
). The anti-inflammatory selectivity index (SI) was greater for conoidecyclic A (1.79) than those displayed by conoidecyclic B and C (1.65–1.68) as well as synthetic anti-inflammatory agents (ibuprofen, 0.44 and sodium salicylate, 0.73) (
<tableCitation id="C6D00338FF82BD4B5E58B8EEE5821B70" box="[826,900,1518,1537]" captionStart="Table 2" captionStartId="6.[100,150,150,166]" captionTargetPageId="6" captionText="Table 2 Bioactivities of conoidecyclics A-C isolated from the organic extract of T. conoides and their molecular descriptors." pageId="5" pageNumber="6">Table 2</tableCitation>
). The lesser selectivity ratio of synthetic anti-inflammatory agents specified the selective inhibition towards COX-1, leading to several side effects (
<bibRefCitation id="EFC34B72FF82BD4B5E8FBB25E2BB1B48" author="Laneuville, O. &amp; Breuer, D. K. &amp; Dewitt, D. L. &amp; Hla, T. &amp; Funk, C. D. &amp; Smith, W. L." box="[1005,1213,1573,1593]" pageId="5" pageNumber="6" pagination="927 - 934" refId="ref15755" refString="Laneuville, O., Breuer, D. K., Dewitt, D. L., Hla, T., Funk, C. D., Smith, W. L., 1994. Differential inhibition of human prostaglandin endoperoxide H synthases- 1 and - 2 by nonsteroidal anti-inflammatory drugs. J. Pharmacol. Exp. Therapeut. 271, 927 - 934." type="journal article" year="1994">Laneuville et al., 1994</bibRefCitation>
). Therefore, it could possibly be concluded that conoidecyclic A, with higher SI and greater specificity towards COX-2 was noteworthy towards the development of selective anti-inflammatory therapeutic lead (
<bibRefCitation id="EFC34B72FF82BD4B59F2BB79E3261BFD" author="Spangler, R. S." box="[1168,1312,1657,1676]" pageId="5" pageNumber="6" pagination="435 - 446" refId="ref17280" refString="Spangler, R. S., 1996. Cyclooxygenase 1 and 2 in rheumatic disease: implications for nonsteroidal anti-inflammatory drug therapy. Semin. Arthritis Rheum. 26, 435 - 446. https: // doi. org / 10.1016 / s 0049 - 0172 (96) 80024 - 2." type="journal article" year="1996">Spangler, 1996</bibRefCitation>
). Conoidecyclic A exhibited significantly greater attenuation properties against ACE-I and PTP-1B (IC 
<subScript id="17D634C6FF82BD4B5EFEBBB8E5A81BB7" attach="left" box="[924,942,1720,1734]" fontSize="6" pageId="5" pageNumber="6">50</subScript>
1.23 and 1.39 mM, respectively) as compared to other studied conoidecyclics (IC 
<subScript id="17D634C6FF82BD4B5949BBD4E23B1B93" attach="left" box="[1067,1085,1748,1762]" fontSize="6" pageId="5" pageNumber="6">50</subScript>
<emphasis id="B926EA91FF82BD4B5927BBCDE2531B91" box="[1093,1109,1741,1760]" italics="true" pageId="5" pageNumber="6">&gt;</emphasis>
1.80 mM) (
<tableCitation id="C6D00338FF82BD4B59AFBBCDE3131B91" box="[1229,1301,1741,1760]" captionStart="Table 2" captionStartId="6.[100,150,150,166]" captionTargetPageId="6" captionText="Table 2 Bioactivities of conoidecyclics A-C isolated from the organic extract of T. conoides and their molecular descriptors." pageId="5" pageNumber="6">Table 2</tableCitation>
). The radical scavenging activities (IC 
<subScript id="17D634C6FF82BD4B5E96BBF0E2291B8F" attach="left" box="[1012,1071,1776,1790]" fontSize="6" pageId="5" pageNumber="6">50DPPH</subScript>
1.20 and IC 
<subScript id="17D634C6FF82BD4B59CEBBF0E2E21B8F" attach="left" box="[1196,1252,1776,1790]" fontSize="6" pageId="5" pageNumber="6">50ABTS</subScript>
1.48 mM) exhibited by conoidecyclic A were greater compared to those displayed by conoidecyclic B (IC 
<subScript id="17D634C6FF82BD4B5EA1BA28E5D31A47" attach="left" box="[963,981,1832,1846]" fontSize="6" pageId="5" pageNumber="6">50</subScript>
1.35–1.54 mM), conoidecyclic C (IC 
<subScript id="17D634C6FF82BD4B584ABA28E33C1A47" attach="left" box="[1320,1338,1832,1846]" fontSize="6" pageId="5" pageNumber="6">50</subScript>
1.54–1.81 mM) and commercially available standards (IC 
<subScript id="17D634C6FF82BD4B59DBBA43E2CD1A20" attach="left" box="[1209,1227,1859,1873]" fontSize="6" pageId="5" pageNumber="6">50</subScript>
1.46–1.69 mM).
</paragraph>
<caption id="DF2D660BFF81BD485D06BD96E2361DB0" pageId="6" pageNumber="7" startId="6.[100,150,150,166]" targetBox="[116,1471,209,744]" targetIsTable="true" targetPageId="6" targetType="table">
<paragraph id="8BED3683FF81BD485D06BD96E6A11DD6" blockId="6.[100,1072,150,193]" box="[100,167,150,167]" pageId="6" pageNumber="7">
<emphasis id="B926EA91FF81BD485D06BD96E6A11DD6" bold="true" box="[100,167,150,167]" pageId="6" pageNumber="7">Table 2</emphasis>
</paragraph>
<paragraph id="8BED3683FF81BD485D06BDB0E2361DB0" blockId="6.[100,1072,150,193]" box="[100,1072,175,193]" pageId="6" pageNumber="7">
Bioactivities of conoidecyclics A-C isolated from the organic extract of 
<taxonomicName id="4C524D00FF81BD485FDDBDB0E51F1DB1" box="[703,793,175,192]" class="Anthozoa" family="Dendrophylliidae" genus="Turbinaria" kingdom="Animalia" order="Scleractinia" pageId="6" pageNumber="7" phylum="Cnidaria" rank="species" species="conoides">
<emphasis id="B926EA91FF81BD485FDDBDB0E51F1DB1" bold="true" box="[703,793,175,192]" italics="true" pageId="6" pageNumber="7">T. conoides</emphasis>
</taxonomicName>
and their molecular descriptors.
</paragraph>
</caption>
<paragraph id="8BED3683FF81BD485D16BDD5E3741F97" pageId="6" pageNumber="7">
<table id="F952C423FF8142B15D16BDD1E3B91F99" box="[116,1471,209,744]" gridcols="6" gridrows="23" pageId="6" pageNumber="7">
<tr id="356234C1FF8142B15D16BDD1E3B91D94" box="[116,1471,209,229]" gridrow="0" pageId="6" pageNumber="7">
<th id="76B35DBDFF8142B15D16BDD1E7491D94" box="[116,335,209,229]" gridcol="0" gridrow="0" pageId="6" pageNumber="7">Bioactivities a (IC; mM) 50</th>
<th id="76B35DBDFF8142B15CF9BDD1E4121D94" box="[411,532,209,229]" gridcol="1" gridrow="0" pageId="6" pageNumber="7">Conoidecyclic A</th>
<th id="76B35DBDFF8142B15F14BDD1E4E81D94" box="[630,750,209,229]" gridcol="2" gridrow="0" pageId="6" pageNumber="7">Conoidecyclic B</th>
<th id="76B35DBDFF8142B15E2DBDD1E5CE1D94" box="[847,968,209,229]" gridcol="3" gridrow="0" pageId="6" pageNumber="7">Conoidecyclic C</th>
<th id="76B35DBDFF8142B1594BBDD1E2BA1D94" box="[1065,1212,209,229]" gridcol="4" gridrow="0" pageId="6" pageNumber="7">Standard</th>
<th id="76B35DBDFF8142B1587FBDD1E3B91D94" box="[1309,1471,209,229]" gridcol="5" gridrow="0" pageId="6" pageNumber="7">Standard</th>
</tr>
<tr id="356234C1FF8142B15D16BDF4E3B91C77" box="[116,1471,244,262]" gridrow="1" pageId="6" pageNumber="7" rowspan-1="1" rowspan-2="1" rowspan-3="1" rowspan-4="1" rowspan-5="1">
<th id="76B35DBDFF8142B15D16BDF4E7491C77" box="[116,335,244,262]" gridcol="0" gridrow="1" pageId="6" pageNumber="7">Antioxidant activities a</th>
</tr>
<tr id="356234C1FF8142B15D16BC0BE3B91C6C" box="[116,1471,267,285]" gridrow="2" pageId="6" pageNumber="7">
<th id="76B35DBDFF8142B15D16BC0BE7491C6C" box="[116,335,267,285]" gridcol="0" gridrow="2" pageId="6" pageNumber="7">DPPH. scavenging activity</th>
<td id="76B35DBDFF8142B15CF9BC0BE4121C6C" box="[411,532,267,285]" gridcol="1" gridrow="2" pageId="6" pageNumber="7">1.20d ± 0.05</td>
<td id="76B35DBDFF8142B15F14BC0BE4E81C6C" box="[630,750,267,285]" gridcol="2" gridrow="2" pageId="6" pageNumber="7">1.35c±0.02</td>
<td id="76B35DBDFF8142B15E2DBC0BE5CE1C6C" box="[847,968,267,285]" gridcol="3" gridrow="2" pageId="6" pageNumber="7">1.54a±0.02</td>
<td id="76B35DBDFF8142B1594BBC0BE2BA1C6C" box="[1065,1212,267,285]" gridcol="4" gridrow="2" pageId="6" pageNumber="7">1.46b ± 0.04 P</td>
<td id="76B35DBDFF8142B1587FBC0BE3B91C6C" box="[1309,1471,267,285]" gridcol="5" gridrow="2" pageId="6" pageNumber="7">1.18d ± 0.03Q</td>
</tr>
<tr id="356234C1FF8142B15D16BC21E3B91C45" box="[116,1471,289,308]" gridrow="3" pageId="6" pageNumber="7">
<th id="76B35DBDFF8142B15D16BC21E7491C45" box="[116,335,289,308]" gridcol="0" gridrow="3" pageId="6" pageNumber="7">ABTS+. scavenging</th>
<td id="76B35DBDFF8142B15CF9BC21E4121C45" box="[411,532,289,308]" gridcol="1" gridrow="3" pageId="6" pageNumber="7">1.48d ± 0.01</td>
<td id="76B35DBDFF8142B15F14BC21E4E81C45" box="[630,750,289,308]" gridcol="2" gridrow="3" pageId="6" pageNumber="7">1.54c±0.02</td>
<td id="76B35DBDFF8142B15E2DBC21E5CE1C45" box="[847,968,289,308]" gridcol="3" gridrow="3" pageId="6" pageNumber="7">1.81a±0.04</td>
<td id="76B35DBDFF8142B1594BBC21E2BA1C45" box="[1065,1212,289,308]" gridcol="4" gridrow="3" pageId="6" pageNumber="7">1.69b ± 0.05P</td>
<td id="76B35DBDFF8142B1587FBC21E3B91C45" box="[1309,1471,289,308]" gridcol="5" gridrow="3" pageId="6" pageNumber="7">1.28e±0.02Q</td>
</tr>
<tr id="356234C1FF8142B15D16BC39E3B91C3B" box="[116,1471,313,330]" gridrow="4" pageId="6" pageNumber="7" rowspan-1="1" rowspan-2="1" rowspan-3="1" rowspan-4="1" rowspan-5="1">
<th id="76B35DBDFF8142B15D16BC39E7491C3B" box="[116,335,313,330]" gridcol="0" gridrow="4" pageId="6" pageNumber="7">Anti-inflammatory activities a</th>
</tr>
<tr id="356234C1FF8142B15D16BC4FE3B91C13" box="[116,1471,335,354]" gridrow="5" pageId="6" pageNumber="7">
<th id="76B35DBDFF8142B15D16BC4FE7491C13" box="[116,335,335,354]" gridcol="0" gridrow="5" pageId="6" pageNumber="7">COX-1 inhibition</th>
<td id="76B35DBDFF8142B15CF9BC4FE4121C13" box="[411,532,335,354]" gridcol="1" gridrow="5" pageId="6" pageNumber="7">3.13 c ±0.04</td>
<td id="76B35DBDFF8142B15F14BC4FE4E81C13" box="[630,750,335,354]" gridcol="2" gridrow="5" pageId="6" pageNumber="7">3.19 c ±0.04</td>
<td id="76B35DBDFF8142B15E2DBC4FE5CE1C13" box="[847,968,335,354]" gridcol="3" gridrow="5" pageId="6" pageNumber="7">3.35b ± 0.06</td>
<td id="76B35DBDFF8142B1594BBC4FE2BA1C13" box="[1065,1212,335,354]" gridcol="4" gridrow="5" pageId="6" pageNumber="7">0.19d ± 0.01Ib</td>
<td id="76B35DBDFF8142B1587FBC4FE3B91C13" box="[1309,1471,335,354]" gridcol="5" gridrow="5" pageId="6" pageNumber="7">12.06 a ±0.05S</td>
</tr>
<tr id="356234C1FF8142B15D16BC66E3B91C09" box="[116,1471,358,376]" gridrow="6" pageId="6" pageNumber="7">
<th id="76B35DBDFF8142B15D16BC66E7491C09" box="[116,335,358,376]" gridcol="0" gridrow="6" pageId="6" pageNumber="7">COX-2 inhibition</th>
<td id="76B35DBDFF8142B15CF9BC66E4121C09" box="[411,532,358,376]" gridcol="1" gridrow="6" pageId="6" pageNumber="7">1.75 c±0.04</td>
<td id="76B35DBDFF8142B15F14BC66E4E81C09" box="[630,750,358,376]" gridcol="2" gridrow="6" pageId="6" pageNumber="7">1.93b ± 0.02</td>
<td id="76B35DBDFF8142B15E2DBC66E5CE1C09" box="[847,968,358,376]" gridcol="3" gridrow="6" pageId="6" pageNumber="7">1.99b ± 0.03</td>
<td id="76B35DBDFF8142B1594BBC66E2BA1C09" box="[1065,1212,358,376]" gridcol="4" gridrow="6" pageId="6" pageNumber="7">0.43d ± 0.02Ib</td>
<td id="76B35DBDFF8142B1587FBC66E3B91C09" box="[1309,1471,358,376]" gridcol="5" gridrow="6" pageId="6" pageNumber="7">16.56 a±0.05S</td>
</tr>
<tr id="356234C1FF8142B15D16BC7DE3B91CFE" box="[116,1471,381,399]" gridrow="7" pageId="6" pageNumber="7">
<th id="76B35DBDFF8142B15D16BC7DE7491CFE" box="[116,335,381,399]" gridcol="0" gridrow="7" pageId="6" pageNumber="7">Selectivity index b</th>
<td id="76B35DBDFF8142B15CF9BC7DE4121CFE" box="[411,532,381,399]" gridcol="1" gridrow="7" pageId="6" pageNumber="7">1.79 a±0.03</td>
<td id="76B35DBDFF8142B15F14BC7DE4E81CFE" box="[630,750,381,399]" gridcol="2" gridrow="7" pageId="6" pageNumber="7">1.65b ± 0.04</td>
<td id="76B35DBDFF8142B15E2DBC7DE5CE1CFE" box="[847,968,381,399]" gridcol="3" gridrow="7" pageId="6" pageNumber="7">1.68b ± 0.02</td>
<td id="76B35DBDFF8142B1594BBC7DE2BA1CFE" box="[1065,1212,381,399]" gridcol="4" gridrow="7" pageId="6" pageNumber="7">0.44d±0.03Ib</td>
<td id="76B35DBDFF8142B1587FBC7DE3B91CFE" box="[1309,1471,381,399]" gridcol="5" gridrow="7" pageId="6" pageNumber="7">0.73 c±0.02S</td>
</tr>
<tr id="356234C1FF8142B15D16BC94E3B91CD7" box="[116,1471,404,422]" gridrow="8" pageId="6" pageNumber="7">
<th id="76B35DBDFF8142B15D16BC94E7491CD7" box="[116,335,404,422]" gridcol="0" gridrow="8" pageId="6" pageNumber="7">5-LOX inhibition</th>
<td id="76B35DBDFF8142B15CF9BC94E4121CD7" box="[411,532,404,422]" gridcol="1" gridrow="8" pageId="6" pageNumber="7">4.24 e±0.06</td>
<td id="76B35DBDFF8142B15F14BC94E4E81CD7" box="[630,750,404,422]" gridcol="2" gridrow="8" pageId="6" pageNumber="7">4.88 c±0.04</td>
<td id="76B35DBDFF8142B15E2DBC94E5CE1CD7" box="[847,968,404,422]" gridcol="3" gridrow="8" pageId="6" pageNumber="7">5.07b ± 0.09</td>
<td id="76B35DBDFF8142B1594BBC94E2BA1CD7" box="[1065,1212,404,422]" gridcol="4" gridrow="8" pageId="6" pageNumber="7">4.51d ± 0.11Ib</td>
<td id="76B35DBDFF8142B1587FBC94E3B91CD7" box="[1309,1471,404,422]" gridcol="5" gridrow="8" pageId="6" pageNumber="7">10.93 a±0.12S</td>
</tr>
<tr id="356234C1FF8142B15D16BCABE3B91CCC" box="[116,1471,427,445]" gridrow="9" pageId="6" pageNumber="7" rowspan-1="1" rowspan-2="1" rowspan-3="1" rowspan-4="1" rowspan-5="1">
<th id="76B35DBDFF8142B15D16BCABE7491CCC" box="[116,335,427,445]" gridcol="0" gridrow="9" pageId="6" pageNumber="7">Anti-hypertensive activity a</th>
</tr>
<tr id="356234C1FF8142B15D16BCC1E3B91CA5" box="[116,1471,449,468]" gridrow="10" pageId="6" pageNumber="7">
<th id="76B35DBDFF8142B15D16BCC1E7491CA5" box="[116,335,449,468]" gridcol="0" gridrow="10" pageId="6" pageNumber="7">ACE-I inhibition</th>
<td id="76B35DBDFF8142B15CF9BCC1E4121CA5" box="[411,532,449,468]" gridcol="1" gridrow="10" pageId="6" pageNumber="7">1.23c±0.02</td>
<td id="76B35DBDFF8142B15F14BCC1E4E81CA5" box="[630,750,449,468]" gridcol="2" gridrow="10" pageId="6" pageNumber="7">1.89b ± 0.04</td>
<td id="76B35DBDFF8142B15E2DBCC1E5CE1CA5" box="[847,968,449,468]" gridcol="3" gridrow="10" pageId="6" pageNumber="7">2.23a±0.02</td>
<td id="76B35DBDFF8142B1594BBCC1E2BA1CA5" box="[1065,1212,449,468]" gridcol="4" gridrow="10" pageId="6" pageNumber="7">0.53d ± 0.02CP</td>
<td id="76B35DBDFF8142B1587FBCC1E3B91CA5" box="[1309,1471,449,468]" gridcol="5" gridrow="10" pageId="6" pageNumber="7">–</td>
</tr>
<tr id="356234C1FF8142B15D16BCD9E3B91C9B" box="[116,1471,473,490]" gridrow="11" pageId="6" pageNumber="7" rowspan-1="1" rowspan-2="1" rowspan-3="1" rowspan-4="1" rowspan-5="1">
<th id="76B35DBDFF8142B15D16BCD9E7491C9B" box="[116,335,473,490]" gridcol="0" gridrow="11" pageId="6" pageNumber="7">Anti-diabetic activity a</th>
</tr>
<tr id="356234C1FF8142B15D16BCEFE3B91F73" box="[116,1471,495,514]" gridrow="12" pageId="6" pageNumber="7">
<th id="76B35DBDFF8142B15D16BCEFE7491F73" box="[116,335,495,514]" gridcol="0" gridrow="12" pageId="6" pageNumber="7">PTP-1B inhibition</th>
<td id="76B35DBDFF8142B15CF9BCEFE4121F73" box="[411,532,495,514]" gridcol="1" gridrow="12" pageId="6" pageNumber="7">1.39 c ±0.03</td>
<td id="76B35DBDFF8142B15F14BCEFE4E81F73" box="[630,750,495,514]" gridcol="2" gridrow="12" pageId="6" pageNumber="7">2.33b ± 0.02</td>
<td id="76B35DBDFF8142B15E2DBCEFE5CE1F73" box="[847,968,495,514]" gridcol="3" gridrow="12" pageId="6" pageNumber="7">3.13 a ±0.04</td>
<td id="76B35DBDFF8142B1594BBCEFE2BA1F73" box="[1065,1212,495,514]" gridcol="4" gridrow="12" pageId="6" pageNumber="7">1.13d ± 0.06SV</td>
<td id="76B35DBDFF8142B1587FBCEFE3B91F73" box="[1309,1471,495,514]" gridcol="5" gridrow="12" pageId="6" pageNumber="7">–</td>
</tr>
<tr id="356234C1FF8142B15D16BF06E3B91F69" box="[116,1471,518,536]" gridrow="13" pageId="6" pageNumber="7">
<th id="76B35DBDFF8142B15D16BF06E7491F69" box="[116,335,518,536]" gridcol="0" gridrow="13" pageId="6" pageNumber="7">Molecular descriptors c</th>
<td id="76B35DBDFF8142B15CF9BF06E4121F69" box="[411,532,518,536]" gridcol="1" gridrow="13" pageId="6" pageNumber="7">Conoidecyclic A</td>
<td id="76B35DBDFF8142B15F14BF06E4E81F69" box="[630,750,518,536]" gridcol="2" gridrow="13" pageId="6" pageNumber="7">Conoidecyclic B</td>
<td id="76B35DBDFF8142B15E2DBF06E5CE1F69" box="[847,968,518,536]" gridcol="3" gridrow="13" pageId="6" pageNumber="7">Conoidecyclic C</td>
<td id="76B35DBDFF8142B1594BBF06E2BA1F69" box="[1065,1212,518,536]" gridcol="4" gridrow="13" pageId="6" pageNumber="7">
<emphasis id="B926EA91FF81BD48594BBF08E2341F69" bold="true" box="[1065,1074,520,536]" italics="true" pageId="6" pageNumber="7">α</emphasis>
-tocopherol (BHT)
</td>
<td id="76B35DBDFF8142B1587FBF06E3B91F69" box="[1309,1471,518,536]" gridcol="5" gridrow="13" pageId="6" pageNumber="7">Ibuprofen (Captopril)</td>
</tr>
<tr id="356234C1FF8142B15D16BF21E3B91F5E" box="[116,1471,545,559]" gridrow="14" pageId="6" pageNumber="7">
<th id="76B35DBDFF8142B15D16BF21E3B91F5E" box="[116,1471,545,559]" colspan="6" colspanRight="5" gridcol="0" gridrow="14" pageId="6" pageNumber="7">Electronic</th>
</tr>
<tr id="356234C1FF8142B15D16BF38E3B91F37" box="[116,1471,568,582]" gridrow="15" pageId="6" pageNumber="7">
<th id="76B35DBDFF8142B15D16BF38E7491F37" box="[116,335,568,582]" gridcol="0" gridrow="15" pageId="6" pageNumber="7">tPSA</th>
<td id="76B35DBDFF8142B15CF9BF38E4121F37" box="[411,532,568,582]" gridcol="1" gridrow="15" pageId="6" pageNumber="7">96.22</td>
<td id="76B35DBDFF8142B15F14BF38E4E81F37" box="[630,750,568,582]" gridcol="2" gridrow="15" pageId="6" pageNumber="7">122.52</td>
<td id="76B35DBDFF8142B15E2DBF38E5CE1F37" box="[847,968,568,582]" gridcol="3" gridrow="15" pageId="6" pageNumber="7">122.52</td>
<td id="76B35DBDFF8142B1594BBF38E2BA1F37" box="[1065,1212,568,582]" gridcol="4" gridrow="15" pageId="6" pageNumber="7">29.46 (20.23)</td>
<td id="76B35DBDFF8142B1587FBF38E3B91F37" box="[1309,1471,568,582]" gridcol="5" gridrow="15" pageId="6" pageNumber="7">37.30 (57.61)</td>
</tr>
<tr id="356234C1FF8142B15D16BF4BE3B91F2C" box="[116,1471,587,605]" gridrow="16" pageId="6" pageNumber="7">
<th id="76B35DBDFF8142B15D16BF4BE7491F2C" box="[116,335,587,605]" gridcol="0" gridrow="16" pageId="6" pageNumber="7">PI (× 10 24 cm3)</th>
<td id="76B35DBDFF8142B15CF9BF4BE4121F2C" box="[411,532,587,605]" gridcol="1" gridrow="16" pageId="6" pageNumber="7">51</td>
<td id="76B35DBDFF8142B15F14BF4BE4E81F2C" box="[630,750,587,605]" gridcol="2" gridrow="16" pageId="6" pageNumber="7">61</td>
<td id="76B35DBDFF8142B15E2DBF4BE5CE1F2C" box="[847,968,587,605]" gridcol="3" gridrow="16" pageId="6" pageNumber="7">55</td>
<td id="76B35DBDFF8142B1594BBF4BE2BA1F2C" box="[1065,1212,587,605]" gridcol="4" gridrow="16" pageId="6" pageNumber="7">53.54 (27.64)</td>
<td id="76B35DBDFF8142B1587FBF4BE3B91F2C" box="[1309,1471,587,605]" gridcol="5" gridrow="16" pageId="6" pageNumber="7">23.96 (21.00)</td>
</tr>
<tr id="356234C1FF8142B15D16BF65E3B91F02" box="[116,1471,613,627]" gridrow="17" pageId="6" pageNumber="7" rowspan-1="1" rowspan-2="1" rowspan-3="1" rowspan-4="1" rowspan-5="1">
<th id="76B35DBDFF8142B15D16BF65E7491F02" box="[116,335,613,627]" gridcol="0" gridrow="17" pageId="6" pageNumber="7">Steric</th>
</tr>
<tr id="356234C1FF8142B15D16BF78E3B91FFB" box="[116,1471,632,650]" gridrow="18" pageId="6" pageNumber="7">
<th id="76B35DBDFF8142B15D16BF78E7491FFB" box="[116,335,632,650]" gridcol="0" gridrow="18" pageId="6" pageNumber="7">MR (cm3/mol)</th>
<td id="76B35DBDFF8142B15CF9BF78E4121FFB" box="[411,532,632,650]" gridcol="1" gridrow="18" pageId="6" pageNumber="7">129.78</td>
<td id="76B35DBDFF8142B15F14BF78E4E81FFB" box="[630,750,632,650]" gridcol="2" gridrow="18" pageId="6" pageNumber="7">154.66</td>
<td id="76B35DBDFF8142B15E2DBF78E5CE1FFB" box="[847,968,632,650]" gridcol="3" gridrow="18" pageId="6" pageNumber="7">140.80</td>
<td id="76B35DBDFF8142B1594BBF78E2BA1FFB" box="[1065,1212,632,650]" gridcol="4" gridrow="18" pageId="6" pageNumber="7">135.6 (69.73)</td>
<td id="76B35DBDFF8142B1587FBF78E3B91FFB" box="[1309,1471,632,650]" gridcol="5" gridrow="18" pageId="6" pageNumber="7">60.44 (54.85)</td>
</tr>
<tr id="356234C1FF8142B15D16BF8FE3B91FD0" box="[116,1471,655,673]" gridrow="19" pageId="6" pageNumber="7">
<th id="76B35DBDFF8142B15D16BF8FE7491FD0" box="[116,335,655,673]" gridcol="0" gridrow="19" pageId="6" pageNumber="7">MV(cm3)</th>
<td id="76B35DBDFF8142B15CF9BF8FE4121FD0" box="[411,532,655,673]" gridcol="1" gridrow="19" pageId="6" pageNumber="7">447.4</td>
<td id="76B35DBDFF8142B15F14BF8FE4E81FD0" box="[630,750,655,673]" gridcol="2" gridrow="19" pageId="6" pageNumber="7">534.9</td>
<td id="76B35DBDFF8142B15E2DBF8FE5CE1FD0" box="[847,968,655,673]" gridcol="3" gridrow="19" pageId="6" pageNumber="7">522.0</td>
<td id="76B35DBDFF8142B1594BBF8FE2BA1FD0" box="[1065,1212,655,673]" gridcol="4" gridrow="19" pageId="6" pageNumber="7">462.70 (237.50)</td>
<td id="76B35DBDFF8142B1587FBF8FE3B91FD0" box="[1309,1471,655,673]" gridcol="5" gridrow="19" pageId="6" pageNumber="7">200.10 (170.7)</td>
</tr>
<tr id="356234C1FF8142B15D16BFA6E3B91FC9" box="[116,1471,678,696]" gridrow="20" pageId="6" pageNumber="7">
<th id="76B35DBDFF8142B15D16BFA6E7491FC9" box="[116,335,678,696]" gridcol="0" gridrow="20" pageId="6" pageNumber="7">P (cm3)</th>
<td id="76B35DBDFF8142B15CF9BFA6E4121FC9" box="[411,532,678,696]" gridcol="1" gridrow="20" pageId="6" pageNumber="7">1092.7</td>
<td id="76B35DBDFF8142B15F14BFA6E4E81FC9" box="[630,750,678,696]" gridcol="2" gridrow="20" pageId="6" pageNumber="7">1316.5</td>
<td id="76B35DBDFF8142B15E2DBFA6E5CE1FC9" box="[847,968,678,696]" gridcol="3" gridrow="20" pageId="6" pageNumber="7">1198.4</td>
<td id="76B35DBDFF8142B1594BBFA6E2BA1FC9" box="[1065,1212,678,696]" gridcol="4" gridrow="20" pageId="6" pageNumber="7">1123.00 (556.00)</td>
<td id="76B35DBDFF8142B1587FBFA6E3B91FC9" box="[1309,1471,678,696]" gridcol="5" gridrow="20" pageId="6" pageNumber="7">499.30 (463.4)</td>
</tr>
<tr id="356234C1FF8142B15D16BFC1E3B91FBE" box="[116,1471,705,719]" gridrow="21" pageId="6" pageNumber="7">
<th id="76B35DBDFF8142B15D16BFC1E3B91FBE" box="[116,1471,705,719]" colspan="6" colspanRight="5" gridcol="0" gridrow="21" pageId="6" pageNumber="7">Hydrophobic</th>
</tr>
<tr id="356234C1FF8142B15D16BFD7E3B91F99" box="[116,1471,727,744]" gridrow="22" pageId="6" pageNumber="7">
<th id="76B35DBDFF8142B15D16BFD7E7491F99" box="[116,335,727,744]" gridcol="0" gridrow="22" pageId="6" pageNumber="7">Log POW</th>
<td id="76B35DBDFF8142B15CF9BFD7E4121F99" box="[411,532,727,744]" gridcol="1" gridrow="22" pageId="6" pageNumber="7">3.13</td>
<td id="76B35DBDFF8142B15F14BFD7E4E81F99" box="[630,750,727,744]" gridcol="2" gridrow="22" pageId="6" pageNumber="7">3.83</td>
<td id="76B35DBDFF8142B15E2DBFD7E5CE1F99" box="[847,968,727,744]" gridcol="3" gridrow="22" pageId="6" pageNumber="7">2.61</td>
<td id="76B35DBDFF8142B1594BBFD7E2BA1F99" box="[1065,1212,727,744]" gridcol="4" gridrow="22" pageId="6" pageNumber="7">9.98 (5.74)</td>
<td id="76B35DBDFF8142B1587FBFD7E3B91F99" box="[1309,1471,727,744]" gridcol="5" gridrow="22" pageId="6" pageNumber="7">3.75 (0.24)</td>
</tr>
</table>
</paragraph>
<tableNote id="76B4370DFF81BD485D06BFFBE6DA1ECE" pageId="6" pageNumber="7" targetBox="[116,1471,209,744]" targetPageId="6">
<paragraph id="8BED3683FF81BD485D06BFFBE79D1E57" blockId="6.[100,1488,763,959]" pageId="6" pageNumber="7">
Different superscripts (P–V) indicate the standards used for different activities; P- 
<emphasis id="B926EA91FF81BD485E71BFFBE5181E7C" bold="true" box="[787,798,763,781]" italics="true" pageId="6" pageNumber="7">α</emphasis>
-Tocopherol; Q-Butylated hydroxy toluene; Ib-Ibuprofen; S-Sodium salicylate; CP- Captopril; SV- Sodium metavandate.
</paragraph>
<paragraph id="8BED3683FF81BD485D11BE2AE5751E28" blockId="6.[100,1488,763,959]" pageId="6" pageNumber="7">
<superScript id="7C279BCBFF81BD485D11BE2AE67C1E47" attach="right" box="[115,122,810,822]" fontSize="5" pageId="6" pageNumber="7">a</superScript>
Bioactivities were expressed as IC values (mM). Samples were analyzed in triplicate (n = 3) and expressed as mean ± standard deviation. Means followed by the 
<subScript id="17D634C6FF81BD485CFFBE35E7AB1E30" attach="left" box="[413,429,821,833]" fontSize="5" pageId="6" pageNumber="7">50</subScript>
different superscripts (a-e) within the same row indicated significant differences (
<emphasis id="B926EA91FF81BD485E78BE48E53C1E28" box="[794,826,840,857]" italics="true" pageId="6" pageNumber="7">
<emphasis id="B926EA91FF81BD485E78BE48E5231E29" bold="true" box="[794,805,840,856]" italics="true" pageId="6" pageNumber="7">P</emphasis>
&lt;
</emphasis>
0.05).
</paragraph>
<paragraph id="8BED3683FF81BD485D11BE5DE5BD1E02" blockId="6.[100,1488,763,959]" box="[115,955,861,883]" pageId="6" pageNumber="7">
<superScript id="7C279BCBFF81BD485D11BE5DE67D1E18" attach="left" box="[115,123,861,873]" fontSize="5" pageId="6" pageNumber="7">b</superScript>
Selectivity index has been calculated as the ratio of anti COX-1(IC) to that of anti COX-2(IC).
</paragraph>
<paragraph id="8BED3683FF81BD485FD4BE68E6DA1ECE" blockId="6.[100,1488,763,959]" pageId="6" pageNumber="7">
<subScript id="17D634C6FF81BD485FD4BE68E5A81E05" attach="left" box="[694,942,872,884]" fontSize="5" pageId="6" pageNumber="7">50 50</subScript>
<superScript id="7C279BCBFF81BD485D11BE76E67C1EF3" attach="right" box="[115,122,886,898]" fontSize="5" pageId="6" pageNumber="7">c</superScript>
Structure-activity relationship analysis was carried out by using different molecular descriptors of the purified compounds as described in the text. tPSA, topological polar surface area; MV, molar volume; P, parachor; MR, molar refractivity; Log POW, logarithmic scale of the octanol-water partition coefficient; PI, polarizability.
</paragraph>
</tableNote>
<paragraph id="8BED3683FF81BD485D06BEE8E7A21967" blockId="6.[100,686,1000,1047]" pageId="6" pageNumber="7">
<heading id="D0A581EFFF81BD485D06BEE8E7A21967" bold="true" fontSize="36" level="1" pageId="6" pageNumber="7" reason="1">
<emphasis id="B926EA91FF81BD485D06BEE8E7A21967" bold="true" italics="true" pageId="6" pageNumber="7">
2.5. Structure-activity correlation study analysis of conoidecyclic analogues isolated from 
<taxonomicName id="4C524D00FF81BD485C5DB904E7A21967" box="[319,420,1027,1047]" class="Anthozoa" family="Dendrophylliidae" genus="Turbinaria" kingdom="Animalia" order="Scleractinia" pageId="6" pageNumber="7" phylum="Cnidaria" rank="species" species="conoides">T. conoides</taxonomicName>
</emphasis>
</heading>
</paragraph>
<paragraph id="8BED3683FF81BD485DE6B93CE6A41B34" blockId="6.[100,771,1084,1605]" pageId="6" pageNumber="7">
The steric factors of the studied compounds might play pivotal roles towards their potential bioactivities. Notably, the electronic properties of conoidecyclic B and C were higher than those of conoidecyclic A (
<tableCitation id="C6D00338FF81BD485D0EB98FE6B519D2" box="[108,179,1167,1187]" captionStart="Table 2" captionStartId="6.[100,150,150,166]" captionTargetPageId="6" captionText="Table 2 Bioactivities of conoidecyclics A-C isolated from the organic extract of T. conoides and their molecular descriptors." pageId="6" pageNumber="7">Table 2</tableCitation>
), even though the bioactivities of the latter were greater. This could be explained by the comparatively lesser steric bulkiness of conoidecyclic A (P 
<quantity id="4CAA9B66FF81BD485C62B9C7E76119AA" box="[256,359,1223,1243]" metricMagnitude="1" metricUnit="m" metricValue="1.0927" pageId="6" pageNumber="7" unit="cm" value="1092.7">1092.7 cm</quantity>
<superScript id="7C279BCBFF81BD485C05B9C1E77619BE" attach="left" box="[359,368,1217,1231]" fontSize="6" pageId="6" pageNumber="7">3</superScript>
, MV 
<quantity id="4CAA9B66FF81BD485CCAB9C7E40519AA" box="[424,515,1223,1243]" metricMagnitude="0" metricUnit="m" metricValue="4.473999999999999" pageId="6" pageNumber="7" unit="cm" value="447.4">447.4 cm</quantity>
<superScript id="7C279BCBFF81BD485F61B9C1E40A19BE" attach="left" box="[515,524,1217,1231]" fontSize="6" pageId="6" pageNumber="7">3</superScript>
) than those recorded for conoidecyclic B (P 
<quantity id="4CAA9B66FF81BD485C7FB9E3E7851987" box="[285,387,1251,1270]" metricMagnitude="1" metricUnit="m" metricValue="1.3165" pageId="6" pageNumber="7" unit="cm" value="1316.5">1316.5 cm</quantity>
<superScript id="7C279BCBFF81BD485CE1B9DDE78A199A" attach="left" box="[387,396,1245,1259]" fontSize="6" pageId="6" pageNumber="7">3</superScript>
, MV 
<quantity id="4CAA9B66FF81BD485CA0B9E3E41A1987" box="[450,540,1251,1270]" metricMagnitude="0" metricUnit="m" metricValue="5.348999999999999" pageId="6" pageNumber="7" unit="cm" value="534.9">534.9 cm</quantity>
<superScript id="7C279BCBFF81BD485F7EB9DDE423199A" attach="left" box="[540,549,1245,1259]" fontSize="6" pageId="6" pageNumber="7">3</superScript>
) and C (P 1198.4, MV 522.0 cm 
<superScript id="7C279BCBFF81BD485DDDB9F9E6CE1876" attach="left" box="[191,200,1273,1287]" fontSize="6" pageId="6" pageNumber="7">3</superScript>
) owing to the presence of bulkier side chain in the latter. These inferences were appropriately corroborated by the efficiency of conoidecyclic A towards the conformationally favorable interaction with the active binding sites of the target enzymes. Notably, the hydrophobicity of conoidecyclic A and B (log POW 3.13–3.83) were found to reside within the permissible limit of hydrophobic-lipophilic threshold (
<bibRefCitation id="EFC34B72FF81BD485DACB8A6E75118C8" author="Lipinski, C. A." box="[206,343,1446,1465]" pageId="6" pageNumber="7" pagination="337 - 341" refId="ref15966" refString="Lipinski, C. A., 2004. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov. Today Technol. 1, 337 - 341. https: // doi. org / 10.1016 / j. ddtec. 2004.11.007." type="journal article" year="2004">Lipinski, 2004</bibRefCitation>
), which could attribute to their prospective bioactive properties. An earlier report of literature inferred that the effective permeability in the cellular network (through inter membrane barrier) along with the radical scavenging activities of the pharmacophore agents might result in their potential bioactivities (
<bibRefCitation id="EFC34B72FF81BD485FEEBB16E6921B34" author="Ishige, K. &amp; Schubert, D. &amp; Sagara, Y." pageId="6" pageNumber="7" pagination="433 - 446" refId="ref15494" refString="Ishige, K., Schubert, D., Sagara, Y., 2001. Flavonoids protect neuronal cells from oxidative stress by three distinct mechanisms. Free Radic. Biol. Med. 30, 433 - 446. https: // doi. org / 10.1016 / s 0891 - 5849 (00) 00498 - 6." type="journal article" year="2001">Ishige et al., 2001</bibRefCitation>
).
</paragraph>
<paragraph id="8BED3683FF81BD485D06BB78E4221BFA" blockId="6.[100,548,1655,1675]" box="[100,548,1655,1675]" pageId="6" pageNumber="7">
<heading id="D0A581EFFF81BD485D06BB78E4221BFA" bold="true" box="[100,548,1655,1675]" fontSize="36" level="1" pageId="6" pageNumber="7" reason="1">
<emphasis id="B926EA91FF81BD485D06BB78E4221BFA" bold="true" box="[100,548,1655,1675]" italics="true" pageId="6" pageNumber="7">2.6. ADME and other physicochemical parametrs</emphasis>
</heading>
</paragraph>
<paragraph id="8BED3683FF81BD485DE6BBAFE24E1B0C" blockId="6.[100,770,1711,1982]" lastBlockId="6.[818,1488,1000,1661]" pageId="6" pageNumber="7">
Swiss ADME tools were used (
<bibRefCitation id="EFC34B72FF81BD485CF5BBAFE43C1BB2" author="Daina, A. &amp; Michielin, O. &amp; Zoete, V." box="[407,570,1711,1731]" pageId="6" pageNumber="7" pagination="42717" refId="ref14855" refString="Daina, A., Michielin, O., Zoete, V., 2017. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep. 7, 42717. https: // doi. org / 10.1038 / srep 42717." type="journal article" year="2017">Daina et al., 2017</bibRefCitation>
) for the estimation of different physicochemical parameters, drug-likeness, solubilities and ADME behaviors of the isolated compounds (conoidecyclics A-C). Based upon the specific physicochemical parameters, the qualitative prediction was performed, and only conoidecyclic A passed the filter of Lipinski’ s rule without any violation, whereas conoidecyclic B and C had one violation (MW
<emphasis id="B926EA91FF81BD485C7FBA57E72B1A1B" box="[285,301,1879,1898]" italics="true" pageId="6" pageNumber="7">&gt;</emphasis>
500) (
<tableCitation id="C6D00338FF81BD485C0DBA57E7B01A1B" box="[367,438,1879,1898]" captionStart="Table 3" captionStartId="7.[100,150,150,166]" captionTargetPageId="7" captionText="Table 3 Physicochemical and pharmacokinetic parameters of conoidecyclics A-C." pageId="6" pageNumber="7">Table 3</tableCitation>
). Therefore, conoidecyclic A could possess greater oral bioavailability. Notably, all the three compounds could pass the filter of Veber rule without any violations (
<tableCitation id="C6D00338FF81BD485FD2BA8FE4FC1AD3" box="[688,762,1935,1954]" captionStart="Table 3" captionStartId="7.[100,150,150,166]" captionTargetPageId="7" captionText="Table 3 Physicochemical and pharmacokinetic parameters of conoidecyclics A-C." pageId="6" pageNumber="7">Table 3</tableCitation>
) (
<bibRefCitation id="EFC34B72FF81BD485D0EBAABE7131ACF" author="Daina, A. &amp; Michielin, O. &amp; Zoete, V." box="[108,277,1963,1982]" pageId="6" pageNumber="7" pagination="42717" refId="ref14855" refString="Daina, A., Michielin, O., Zoete, V., 2017. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep. 7, 42717. https: // doi. org / 10.1038 / srep 42717." type="journal article" year="2017">Daina et al., 2017</bibRefCitation>
). In addition to that, predicted bioavailability score for the studied compounds were comparable (0.55) with that of ibuprofen (0.55), which apparently recognized at least 10% oral bioavailability in rat and permeability towards Caco-2 cell lines (
<bibRefCitation id="EFC34B72FF81BD4858FAB920E5A7193E" author="Daina, A. &amp; Michielin, O. &amp; Zoete, V." pageId="6" pageNumber="7" pagination="42717" refId="ref14855" refString="Daina, A., Michielin, O., Zoete, V., 2017. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep. 7, 42717. https: // doi. org / 10.1038 / srep 42717." type="journal article" year="2017">Daina et al., 2017</bibRefCitation>
) (
<tableCitation id="C6D00338FF81BD485EDBB93CE204193E" box="[953,1026,1084,1103]" captionStart="Table 3" captionStartId="7.[100,150,150,166]" captionTargetPageId="7" captionText="Table 3 Physicochemical and pharmacokinetic parameters of conoidecyclics A-C." pageId="6" pageNumber="7">Table 3</tableCitation>
). For the rapid estimation of drug-likeness, the bioavailability radar plot was adopted, and six physicochemical parameters (size, lipophilicity, polarity, flexibility, solubility and saturation) were taken into account (Fig. S34). The optimum range for each parameter was shown by a pink area. Evidently, conoidecyclic B and C displayed a deviation including larger size (MW
<emphasis id="B926EA91FF81BD485991B9C7E30519AB" box="[1267,1283,1223,1242]" italics="true" pageId="6" pageNumber="7">&gt;</emphasis>
500), even though no eccentricity was apparent for conoidecyclic A, and all the six values (comparing to ibuprofen, conoidecyclic A exhibited lesser flexibility) led to optimal physicochemical attributes leading to an acceptable oral bioavailability. Solubility is considered to be one of the vital parameters for drug development activities, and also related to absorption (
<bibRefCitation id="EFC34B72FF81BD4858FAB853E59C18F3" author="Daina, A. &amp; Michielin, O. &amp; Zoete, V." pageId="6" pageNumber="7" pagination="42717" refId="ref14855" refString="Daina, A., Michielin, O., Zoete, V., 2017. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep. 7, 42717. https: // doi. org / 10.1038 / srep 42717." type="journal article" year="2017">Daina et al., 2017</bibRefCitation>
). Estimated aqueous solubility (Log S; ESOL and SILICOS-IT) for three isolated compounds based on molecular structure were in a range of moderately soluble to soluble (
<tableCitation id="C6D00338FF81BD4859FCB8A6E2E518C8" box="[1182,1251,1446,1465]" captionStart="Table 3" captionStartId="7.[100,150,150,166]" captionTargetPageId="7" captionText="Table 3 Physicochemical and pharmacokinetic parameters of conoidecyclics A-C." pageId="6" pageNumber="7">Table 3</tableCitation>
). Logarithm value of skin permeability coefficient 
<subScript id="17D634C6FF81BD485943B8C3E23E18A9" attach="left" box="[1057,1080,1475,1496]" fontSize="6" pageId="6" pageNumber="7">Kp</subScript>
(regarding pharmacokinetics) was calculated for the isolated compounds including the standard (ibuprofen), whereas more negative value of 
<subScript id="17D634C6FF81BD485939B8FAE2741B61" attach="left" box="[1115,1138,1530,1552]" fontSize="6" pageId="6" pageNumber="7">Kp</subScript>
inferred lesser skin permeability. The latter could be linearly correlated with the molecular size, lipophilicity, and it was observed that conoidecyclic A exhibited a 
<subScript id="17D634C6FF81BD485854BB32E34A1B36" attach="left" box="[1334,1356,1586,1607]" fontSize="6" pageId="6" pageNumber="7">Kp</subScript>
value (- 
<quantity id="4CAA9B66FF81BD4858C7BB32E5541B10" metricMagnitude="-2" metricUnit="m" metricValue="6.51" pageId="6" pageNumber="7" unit="cm" value="6.51">6.51 cm</quantity>
/s) closer to that exhibited by conoidecyclic B and C (- 6.56 and - 
<quantity id="4CAA9B66FF81BD4858C7BB4EE5551B0C" metricMagnitude="-2" metricUnit="m" metricValue="7.25" pageId="6" pageNumber="7" unit="cm" value="7.25">7.25 cm</quantity>
/s, respectively) (
<tableCitation id="C6D00338FF81BD485E91BB69E23C1B0C" box="[1011,1082,1641,1661]" captionStart="Table 3" captionStartId="7.[100,150,150,166]" captionTargetPageId="7" captionText="Table 3 Physicochemical and pharmacokinetic parameters of conoidecyclics A-C." pageId="6" pageNumber="7">Table 3</tableCitation>
).
</paragraph>
<paragraph id="8BED3683FF81BD485E50BBAFE36E1BB3" blockId="6.[818,1384,1711,1730]" box="[818,1384,1711,1730]" pageId="6" pageNumber="7">
<heading id="D0A581EFFF81BD485E50BBAFE36E1BB3" bold="true" box="[818,1384,1711,1730]" fontSize="36" level="1" pageId="6" pageNumber="7" reason="1">
<emphasis id="B926EA91FF81BD485E50BBAFE36E1BB3" bold="true" box="[818,1384,1711,1730]" italics="true" pageId="6" pageNumber="7">
2.7. Kinetic properties of ACE-I, PTP-1B and 5- 
<collectionCode id="ED43AE46FF81BD485981BBAFE30B1BB3" box="[1251,1293,1711,1730]" pageId="6" pageNumber="7">LOX</collectionCode>
inhibition
</emphasis>
</heading>
</paragraph>
<paragraph id="8BED3683FF81BD495E33BBE7E6F01B8A" blockId="6.[818,1487,1767,1984]" lastBlockId="7.[100,770,1517,1787]" lastPageId="7" lastPageNumber="8" pageId="6" pageNumber="7">
Kinetic studies were performed to determine the mode of inhibition of conoidecyclics A-C, and the inhibition constants (
<subScript id="17D634C6FF81BD485872BA03E3231A69" attach="left" box="[1296,1317,1795,1816]" fontSize="6" pageId="6" pageNumber="7">Ki</subScript>
) were determined by Lineweaver-Burk and Dixon plots. Conoidecyclics were found to inhibit ACE-I, PTP-1B and 5- 
<collectionCode id="ED43AE46FF81BD485955BA3BE2621A3F" box="[1079,1124,1851,1870]" pageId="6" pageNumber="7">LOX</collectionCode>
enzymes, in a non-competitive fashion as determined by the Lineweaver-Burk plot (Fig. S35). Increase of substrate concentrations could result in non-intersect series of line on Y-axis in the Lineweaver-Burk plot (Fig. S35) but intersected on the negative X axis (
<subScript id="17D634C6FF81BD485E07BAABE57F1AB1" attach="left" box="[869,889,1963,1984]" fontSize="6" pageId="6" pageNumber="7">Ki</subScript>
) in the Dixon plots (
<figureCitation id="13692A06FF81BD485928BAABE2871ACF" box="[1098,1153,1963,1982]" captionStart="Fig" captionStartId="10.[100,130,1176,1193]" captionTargetBox="[116,1469,152,1141]" captionTargetId="figure-496@10.[112,1476,148,1149]" captionTargetPageId="10" captionText="Fig. 6. Kinetic studies of the pharmacologic response with regard to inhibition mode of ACE-I (A–C), PTP-1B (D–F) and 5-LOX (G–I), respectively to the studied conoidecyclics A-C. Representation of Dixon plots for conoidecyclics A-C, for the determination of the inhibition constant Ki. The Ki value was determined from the negative X-axis value at the point of the intersection of the four lines. The data were expressed as the mean reciprocal of initial velocity for triplicates (n = 3) at each substrate concentration. Different concentrations of isolated compounds were used, and the inhibitory potentials were expressed in mM." figureDoi="http://doi.org/10.5281/zenodo.8258132" httpUri="https://zenodo.org/record/8258132/files/figure.png" pageId="6" pageNumber="7">Fig. 6</figureCitation>
). Conoidecyclic A exhibited lesser inhibition constant towards inhibition of ACE-I (1.1 mM), PTP-1B (1.2 mM) and 5- 
<collectionCode id="ED43AE46FF80BD495DB1BB09E7061B6D" box="[211,256,1545,1564]" pageId="7" pageNumber="8">LOX</collectionCode>
(4.0 mM) than those displayed by other studied metabolites (
<figureCitation id="13692A06FF80BD495DA7BB25E6FA1B49" box="[197,252,1573,1592]" captionStart="Fig" captionStartId="10.[100,130,1176,1193]" captionTargetBox="[116,1469,152,1141]" captionTargetId="figure-496@10.[112,1476,148,1149]" captionTargetPageId="10" captionText="Fig. 6. Kinetic studies of the pharmacologic response with regard to inhibition mode of ACE-I (A–C), PTP-1B (D–F) and 5-LOX (G–I), respectively to the studied conoidecyclics A-C. Representation of Dixon plots for conoidecyclics A-C, for the determination of the inhibition constant Ki. The Ki value was determined from the negative X-axis value at the point of the intersection of the four lines. The data were expressed as the mean reciprocal of initial velocity for triplicates (n = 3) at each substrate concentration. Different concentrations of isolated compounds were used, and the inhibitory potentials were expressed in mM." figureDoi="http://doi.org/10.5281/zenodo.8258132" httpUri="https://zenodo.org/record/8258132/files/figure.png" pageId="7" pageNumber="8">Fig. 6</figureCitation>
). An inverse relation of 
<subScript id="17D634C6FF80BD495C89BB26E4111B4A" attach="left" box="[491,535,1574,1595]" fontSize="6" pageId="7" pageNumber="8">Vmax</subScript>
with various concentrations of conoidecyclics A-C inferred the non-competitive inhibition of the target enzymes (
<bibRefCitation id="EFC34B72FF80BD495C4BBB5DE78A1B01" author="Blat, Y." box="[297,396,1629,1648]" pageId="7" pageNumber="8" pagination="535 - 540" refId="ref14342" refString="Blat, Y., 2010. Non-competitive inhibition by active site binders. Chem. Biol. Drug Des. 75, 535 - 540. https: // doi. org / 10.1111 / j. 1747 - 0285.2010.00972. x." type="journal article" year="2010">Blat, 2010</bibRefCitation>
). Among the studied metabolites, conoidecyclic A exhibited lesser apparent 
<subScript id="17D634C6FF80BD495CB1BB79E4061BFE" attach="left" box="[467,512,1657,1679]" fontSize="6" pageId="7" pageNumber="8">Vmax</subScript>
(0.31–0.14, 0.29–0.17 and 0.32–0.17 ΔA min 
<superScript id="7C279BCBFF80BD495C43BB8FE72C1BEC" attach="right" box="[289,298,1679,1693]" fontSize="6" pageId="7" pageNumber="8">1</superScript>
for ACE-I, PTP-1B and 5- 
<collectionCode id="ED43AE46FF80BD495F42BB95E44B1BD9" box="[544,589,1685,1704]" pageId="7" pageNumber="8">LOX</collectionCode>
inhibition, respectively) (
<tableCitation id="C6D00338FF80BD495DCCBBB1E6F81BB5" box="[174,254,1713,1732]" captionStart="Table 2" captionStartId="6.[100,150,150,166]" captionTargetPageId="6" captionText="Table 2 Bioactivities of conoidecyclics A-C isolated from the organic extract of T. conoides and their molecular descriptors." pageId="7" pageNumber="8">Table S2</tableCitation>
) than other studied macrolides, which implied that the former could efficiently bind with targeted enzyme to diminish the reaction velocity.
</paragraph>
<caption id="DF2D660BFF80BD495D06BD96E4D61DB0" pageId="7" pageNumber="8" startId="7.[100,150,150,166]" targetBox="[116,751,213,1234]" targetIsTable="true" targetPageId="7" targetType="table">
<paragraph id="8BED3683FF80BD495D06BD96E6A11DD6" blockId="7.[100,720,150,193]" box="[100,167,150,167]" pageId="7" pageNumber="8">
<emphasis id="B926EA91FF80BD495D06BD96E6A11DD6" bold="true" box="[100,167,150,167]" pageId="7" pageNumber="8">Table 3</emphasis>
</paragraph>
<paragraph id="8BED3683FF80BD495D06BDB0E4D61DB0" blockId="7.[100,720,150,193]" box="[100,720,176,193]" pageId="7" pageNumber="8">Physicochemical and pharmacokinetic parameters of conoidecyclics A-C.</paragraph>
</caption>
<paragraph id="8BED3683FF80BD495D16BDD5E6E619A3" pageId="7" pageNumber="8">
<table id="F952C423FF8042B15D16BDD5E4E919A3" box="[116,751,213,1234]" gridcols="4" gridrows="44" pageId="7" pageNumber="8">
<tr id="356234C1FF8042B15D16BDD5E4E91D92" box="[116,751,213,227]" gridrow="0" pageId="7" pageNumber="8">
<th id="76B35DBDFF8042B15D16BDD5E6FF1D92" box="[116,249,213,227]" gridcol="0" gridrow="0" pageId="7" pageNumber="8">Parameters</th>
<th id="76B35DBDFF8042B15C6DBDD5E78B1D92" box="[271,397,213,227]" gridcol="1" gridrow="0" pageId="7" pageNumber="8">Conoidecyclic A</th>
<th id="76B35DBDFF8042B15CD0BDD5E4461D92" box="[434,576,213,227]" gridcol="2" gridrow="0" pageId="7" pageNumber="8">Conoidecyclic B</th>
<th id="76B35DBDFF8042B15F03BDD5E4E91D92" box="[609,751,213,227]" gridcol="3" gridrow="0" pageId="7" pageNumber="8">Conoidecyclic C</th>
</tr>
<tr id="356234C1FF8042B15D16BDF8E4E91C77" box="[116,751,248,262]" gridrow="1" pageId="7" pageNumber="8">
<th id="76B35DBDFF8042B15D16BDF8E4E91C77" box="[116,751,248,262]" colspan="4" colspanRight="3" gridcol="0" gridrow="1" pageId="7" pageNumber="8">Physicochemical properties</th>
</tr>
<tr id="356234C1FF8042B15D16BC1BE4E91C5A" box="[116,751,283,299]" gridrow="2" pageId="7" pageNumber="8">
<th id="76B35DBDFF8042B15D16BC1BE6FF1C5A" box="[116,249,283,299]" gridcol="0" gridrow="2" pageId="7" pageNumber="8">Formula</th>
<td id="76B35DBDFF8042B15C6DBC1BE78B1C5A" box="[271,397,283,299]" gridcol="1" gridrow="2" pageId="7" pageNumber="8">C27H44O6</td>
<td id="76B35DBDFF8042B15CD0BC1BE4461C5A" box="[434,576,283,299]" gridcol="2" gridrow="2" pageId="7" pageNumber="8">C32H52O8</td>
<td id="76B35DBDFF8042B15F03BC1BE4E91C5A" box="[609,751,283,299]" gridcol="3" gridrow="2" pageId="7" pageNumber="8">C29H46O8</td>
</tr>
<tr id="356234C1FF8042B15D16BC32E4E91C31" box="[116,751,306,320]" gridrow="3" pageId="7" pageNumber="8">
<th id="76B35DBDFF8042B15D16BC32E6FF1C31" box="[116,249,306,320]" gridcol="0" gridrow="3" pageId="7" pageNumber="8">Molecular</th>
<td id="76B35DBDFF8042B15C6DBC32E78B1C31" box="[271,397,306,320]" gridcol="1" gridrow="3" pageId="7" pageNumber="8">464.63 g/mol</td>
<td id="76B35DBDFF8042B15CD0BC32E4461C31" box="[434,576,306,320]" gridcol="2" gridrow="3" pageId="7" pageNumber="8">564.75 g/mol</td>
<td id="76B35DBDFF8042B15F03BC32E4E91C31" box="[609,751,306,320]" gridcol="3" gridrow="3" pageId="7" pageNumber="8">522.67 g/mol</td>
</tr>
<tr id="356234C1FF8042B15D16BC48E4E91C27" box="[116,751,328,342]" gridrow="4" pageId="7" pageNumber="8" rowspan-1="1" rowspan-2="1" rowspan-3="1">
<th id="76B35DBDFF8042B15D16BC48E6FF1C27" box="[116,249,328,342]" gridcol="0" gridrow="4" pageId="7" pageNumber="8">weight</th>
</tr>
<tr id="356234C1FF8042B15D16BC5FE4E91C1F" box="[116,751,351,366]" gridrow="5" pageId="7" pageNumber="8">
<th id="76B35DBDFF8042B15D16BC5FE6FF1C1F" box="[116,249,351,366]" gridcol="0" gridrow="5" pageId="7" pageNumber="8">Num. heavy</th>
<td id="76B35DBDFF8042B15C6DBC5FE78B1C1F" box="[271,397,351,366]" gridcol="1" gridrow="5" pageId="7" pageNumber="8">33</td>
<td id="76B35DBDFF8042B15CD0BC5FE4461C1F" box="[434,576,351,366]" gridcol="2" gridrow="5" pageId="7" pageNumber="8">40</td>
<td id="76B35DBDFF8042B15F03BC5FE4E91C1F" box="[609,751,351,366]" gridcol="3" gridrow="5" pageId="7" pageNumber="8">37</td>
</tr>
<tr id="356234C1FF8042B15D16BC76E4E91CF5" box="[116,751,374,388]" gridrow="6" pageId="7" pageNumber="8" rowspan-1="1" rowspan-2="1" rowspan-3="1">
<th id="76B35DBDFF8042B15D16BC76E6FF1CF5" box="[116,249,374,388]" gridcol="0" gridrow="6" pageId="7" pageNumber="8">atoms</th>
</tr>
<tr id="356234C1FF8042B15D16BC8DE4E91CEA" box="[116,751,397,411]" gridrow="7" pageId="7" pageNumber="8">
<th id="76B35DBDFF8042B15D16BC8DE6FF1CEA" box="[116,249,397,411]" gridcol="0" gridrow="7" pageId="7" pageNumber="8">Fraction Csp 3</th>
<td id="76B35DBDFF8042B15C6DBC8DE78B1CEA" box="[271,397,397,411]" gridcol="1" gridrow="7" pageId="7" pageNumber="8">0.74</td>
<td id="76B35DBDFF8042B15CD0BC8DE4461CEA" box="[434,576,397,411]" gridcol="2" gridrow="7" pageId="7" pageNumber="8">0.75</td>
<td id="76B35DBDFF8042B15F03BC8DE4E91CEA" box="[609,751,397,411]" gridcol="3" gridrow="7" pageId="7" pageNumber="8">0.72</td>
</tr>
<tr id="356234C1FF8042B15D16BCA4E4E91CC3" box="[116,751,420,434]" gridrow="8" pageId="7" pageNumber="8">
<th id="76B35DBDFF8042B15D16BCA4E6FF1CC3" box="[116,249,420,434]" gridcol="0" gridrow="8" pageId="7" pageNumber="8">Num. rotatable</th>
<td id="76B35DBDFF8042B15C6DBCA4E78B1CC3" box="[271,397,420,434]" gridcol="1" gridrow="8" pageId="7" pageNumber="8">1</td>
<td id="76B35DBDFF8042B15CD0BCA4E4461CC3" box="[434,576,420,434]" gridcol="2" gridrow="8" pageId="7" pageNumber="8">6</td>
<td id="76B35DBDFF8042B15F03BCA4E4E91CC3" box="[609,751,420,434]" gridcol="3" gridrow="8" pageId="7" pageNumber="8">4</td>
</tr>
<tr id="356234C1FF8042B15D16BCBBE4E91CB8" box="[116,751,443,457]" gridrow="9" pageId="7" pageNumber="8" rowspan-1="1" rowspan-2="1" rowspan-3="1">
<th id="76B35DBDFF8042B15D16BCBBE6FF1CB8" box="[116,249,443,457]" gridcol="0" gridrow="9" pageId="7" pageNumber="8">bonds</th>
</tr>
<tr id="356234C1FF8042B15D16BCD1E4E91C91" box="[116,751,465,480]" gridrow="10" pageId="7" pageNumber="8">
<th id="76B35DBDFF8042B15D16BCD1E6FF1C91" box="[116,249,465,480]" gridcol="0" gridrow="10" pageId="7" pageNumber="8">Num. H-bond</th>
<td id="76B35DBDFF8042B15C6DBCD1E78B1C91" box="[271,397,465,480]" gridcol="1" gridrow="10" pageId="7" pageNumber="8">6</td>
<td id="76B35DBDFF8042B15CD0BCD1E4461C91" box="[434,576,465,480]" gridcol="2" gridrow="10" pageId="7" pageNumber="8">8</td>
<td id="76B35DBDFF8042B15F03BCD1E4E91C91" box="[609,751,465,480]" gridcol="3" gridrow="10" pageId="7" pageNumber="8">8</td>
</tr>
<tr id="356234C1FF8042B15D16BCE9E4E91C86" box="[116,751,489,503]" gridrow="11" pageId="7" pageNumber="8" rowspan-1="1" rowspan-2="1" rowspan-3="1">
<th id="76B35DBDFF8042B15D16BCE9E6FF1C86" box="[116,249,489,503]" gridcol="0" gridrow="11" pageId="7" pageNumber="8">acceptors</th>
</tr>
<tr id="356234C1FF8042B15D16BCFFE4E91F7F" box="[116,751,511,526]" gridrow="12" pageId="7" pageNumber="8">
<th id="76B35DBDFF8042B15D16BCFFE6FF1F7F" box="[116,249,511,526]" gridcol="0" gridrow="12" pageId="7" pageNumber="8">Num. H-bond</th>
<td id="76B35DBDFF8042B15C6DBCFFE78B1F7F" box="[271,397,511,526]" gridcol="1" gridrow="12" pageId="7" pageNumber="8">3</td>
<td id="76B35DBDFF8042B15CD0BCFFE4461F7F" box="[434,576,511,526]" gridcol="2" gridrow="12" pageId="7" pageNumber="8">3</td>
<td id="76B35DBDFF8042B15F03BCFFE4E91F7F" box="[609,751,511,526]" gridcol="3" gridrow="12" pageId="7" pageNumber="8">3</td>
</tr>
<tr id="356234C1FF8042B15D16BF16E4E91F55" box="[116,751,534,548]" gridrow="13" pageId="7" pageNumber="8" rowspan-1="1" rowspan-2="1" rowspan-3="1">
<th id="76B35DBDFF8042B15D16BF16E6FF1F55" box="[116,249,534,548]" gridcol="0" gridrow="13" pageId="7" pageNumber="8">donors</th>
</tr>
<tr id="356234C1FF8042B15D16BF2DE4E91F4A" box="[116,751,557,571]" gridrow="14" pageId="7" pageNumber="8">
<th id="76B35DBDFF8042B15D16BF2DE6FF1F4A" box="[116,249,557,571]" gridcol="0" gridrow="14" pageId="7" pageNumber="8">Molar</th>
<td id="76B35DBDFF8042B15C6DBF2DE78B1F4A" box="[271,397,557,571]" gridcol="1" gridrow="14" pageId="7" pageNumber="8">132.11</td>
<td id="76B35DBDFF8042B15CD0BF2DE4461F4A" box="[434,576,557,571]" gridcol="2" gridrow="14" pageId="7" pageNumber="8">157.43</td>
<td id="76B35DBDFF8042B15F03BF2DE4E91F4A" box="[609,751,557,571]" gridcol="3" gridrow="14" pageId="7" pageNumber="8">143.01</td>
</tr>
<tr id="356234C1FF8042B15D16BF44E4E91F23" box="[116,751,580,594]" gridrow="15" pageId="7" pageNumber="8" rowspan-1="1" rowspan-2="1" rowspan-3="1">
<th id="76B35DBDFF8042B15D16BF44E6FF1F23" box="[116,249,580,594]" gridcol="0" gridrow="15" pageId="7" pageNumber="8">refractivity</th>
</tr>
<tr id="356234C1FF8042B15D16BF57E4E91F18" box="[116,751,599,617]" gridrow="16" pageId="7" pageNumber="8">
<th id="76B35DBDFF8042B15D16BF57E6FF1F18" box="[116,249,599,617]" gridcol="0" gridrow="16" pageId="7" pageNumber="8">TPSA a</th>
<td id="76B35DBDFF8042B15C6DBF57E78B1F18" box="[271,397,599,617]" gridcol="1" gridrow="16" pageId="7" pageNumber="8">96.22 Å2</td>
<td id="76B35DBDFF8042B15CD0BF57E4461F18" box="[434,576,599,617]" gridcol="2" gridrow="16" pageId="7" pageNumber="8">122.52 Å2</td>
<td id="76B35DBDFF8042B15F03BF57E4E91F18" box="[609,751,599,617]" gridcol="3" gridrow="16" pageId="7" pageNumber="8">122.52 Å2</td>
</tr>
<tr id="356234C1FF8042B15D16BF71E4E91F0E" box="[116,751,625,639]" gridrow="17" pageId="7" pageNumber="8" rowspan-1="1" rowspan-2="1" rowspan-3="1">
<th id="76B35DBDFF8042B15D16BF71E6FF1F0E" box="[116,249,625,639]" gridcol="0" gridrow="17" pageId="7" pageNumber="8">Lipophilicity</th>
</tr>
<tr id="356234C1FF8042B15D16BF84E4E91FE8" box="[116,751,644,665]" gridrow="18" pageId="7" pageNumber="8">
<th id="76B35DBDFF8042B15D16BF84E6FF1FE8" box="[116,249,644,665]" gridcol="0" gridrow="18" pageId="7" pageNumber="8">Log Pb o/w</th>
<td id="76B35DBDFF8042B15C6DBF84E78B1FE8" box="[271,397,644,665]" gridcol="1" gridrow="18" pageId="7" pageNumber="8">3.95</td>
<td id="76B35DBDFF8042B15CD0BF84E4461FE8" box="[434,576,644,665]" gridcol="2" gridrow="18" pageId="7" pageNumber="8">4.31</td>
<td id="76B35DBDFF8042B15F03BF84E4E91FE8" box="[609,751,644,665]" gridcol="3" gridrow="18" pageId="7" pageNumber="8">4.38</td>
</tr>
<tr id="356234C1FF8042B15D16BF9FE4E91FDC" box="[116,751,671,685]" gridrow="19" pageId="7" pageNumber="8" rowspan-1="1" rowspan-2="1" rowspan-3="1">
<th id="76B35DBDFF8042B15D16BF9FE6FF1FDC" box="[116,249,671,685]" gridcol="0" gridrow="19" pageId="7" pageNumber="8">(iLOGP)</th>
</tr>
<tr id="356234C1FF8042B15D16BFB6E4E91FB6" box="[116,751,694,711]" gridrow="20" pageId="7" pageNumber="8">
<th id="76B35DBDFF8042B15D16BFB6E6FF1FB6" box="[116,249,694,711]" gridcol="0" gridrow="20" pageId="7" pageNumber="8">Log Po/w</th>
<td id="76B35DBDFF8042B15C6DBFB6E78B1FB6" box="[271,397,694,711]" gridcol="1" gridrow="20" pageId="7" pageNumber="8">3.70</td>
<td id="76B35DBDFF8042B15CD0BFB6E4461FB6" box="[434,576,694,711]" gridcol="2" gridrow="20" pageId="7" pageNumber="8">4.49</td>
<td id="76B35DBDFF8042B15F03BFB6E4E91FB6" box="[609,751,694,711]" gridcol="3" gridrow="20" pageId="7" pageNumber="8">3.15</td>
</tr>
<tr id="356234C1FF8042B15D16BFCDE4E91FAA" box="[116,751,717,731]" gridrow="21" pageId="7" pageNumber="8" rowspan-1="1" rowspan-2="1" rowspan-3="1">
<th id="76B35DBDFF8042B15D16BFCDE6FF1FAA" box="[116,249,717,731]" gridcol="0" gridrow="21" pageId="7" pageNumber="8">(XLOGP3)</th>
</tr>
<tr id="356234C1FF8042B15D16BFE4E4E91F85" box="[116,751,740,756]" gridrow="22" pageId="7" pageNumber="8">
<th id="76B35DBDFF8042B15D16BFE4E6FF1F85" box="[116,249,740,756]" gridcol="0" gridrow="22" pageId="7" pageNumber="8">Log Po/w</th>
<td id="76B35DBDFF8042B15C6DBFE4E78B1F85" box="[271,397,740,756]" gridcol="1" gridrow="22" pageId="7" pageNumber="8">4.52</td>
<td id="76B35DBDFF8042B15CD0BFE4E4461F85" box="[434,576,740,756]" gridcol="2" gridrow="22" pageId="7" pageNumber="8">5.09</td>
<td id="76B35DBDFF8042B15F03BFE4E4E91F85" box="[609,751,740,756]" gridcol="3" gridrow="22" pageId="7" pageNumber="8">4.06</td>
</tr>
<tr id="356234C1FF8042B15D16BFFBE4E91E78" box="[116,751,763,777]" gridrow="23" pageId="7" pageNumber="8" rowspan-1="1" rowspan-2="1" rowspan-3="1">
<th id="76B35DBDFF8042B15D16BFFBE6FF1E78" box="[116,249,763,777]" gridcol="0" gridrow="23" pageId="7" pageNumber="8">(WLOGP)</th>
</tr>
<tr id="356234C1FF8042B15D16BE11E4E91E51" box="[116,751,785,800]" gridrow="24" pageId="7" pageNumber="8">
<th id="76B35DBDFF8042B15D16BE11E6FF1E51" box="[116,249,785,800]" gridcol="0" gridrow="24" pageId="7" pageNumber="8">Consensus Log</th>
<td id="76B35DBDFF8042B15C6DBE11E78B1E51" box="[271,397,785,800]" gridcol="1" gridrow="24" pageId="7" pageNumber="8">4.05</td>
<td id="76B35DBDFF8042B15CD0BE11E4461E51" box="[434,576,785,800]" gridcol="2" gridrow="24" pageId="7" pageNumber="8">4.63</td>
<td id="76B35DBDFF8042B15F03BE11E4E91E51" box="[609,751,785,800]" gridcol="3" gridrow="24" pageId="7" pageNumber="8">3.86</td>
</tr>
<tr id="356234C1FF8042B15D16BE29E4E91E48" box="[116,751,809,825]" gridrow="25" pageId="7" pageNumber="8" rowspan-1="1" rowspan-2="1" rowspan-3="1">
<th id="76B35DBDFF8042B15D16BE29E6FF1E48" box="[116,249,809,825]" gridcol="0" gridrow="25" pageId="7" pageNumber="8">Po/w</th>
</tr>
<tr id="356234C1FF8042B15D16BE3FE4E91E3C" box="[116,751,831,845]" gridrow="26" pageId="7" pageNumber="8" rowspan-1="1" rowspan-2="1" rowspan-3="1">
<th id="76B35DBDFF8042B15D16BE3FE6FF1E3C" box="[116,249,831,845]" gridcol="0" gridrow="26" pageId="7" pageNumber="8">Water solubility</th>
</tr>
<tr id="356234C1FF8042B15D16BE52E4E91E15" box="[116,751,850,868]" gridrow="27" pageId="7" pageNumber="8">
<th id="76B35DBDFF8042B15D16BE52E6FF1E15" box="[116,249,850,868]" gridcol="0" gridrow="27" pageId="7" pageNumber="8">Log S c (ESOL)</th>
<td id="76B35DBDFF8042B15C6DBE52E78B1E15" box="[271,397,850,868]" gridcol="1" gridrow="27" pageId="7" pageNumber="8">4.99,</td>
<td id="76B35DBDFF8042B15CD0BE52E4461E15" box="[434,576,850,868]" gridcol="2" gridrow="27" pageId="7" pageNumber="8">5.77, moderately</td>
<td id="76B35DBDFF8042B15F03BE52E4E91E15" box="[609,751,850,868]" gridcol="3" gridrow="27" pageId="7" pageNumber="8">4.80, moderately</td>
</tr>
<tr id="356234C1FF8042B15D16BE6DE4E91E0A" box="[116,751,877,891]" gridrow="28" pageId="7" pageNumber="8" rowspan-0="1">
<td id="76B35DBDFF8042B15C6DBE6DE78B1E0A" box="[271,397,877,891]" gridcol="1" gridrow="28" pageId="7" pageNumber="8">moderately</td>
<td id="76B35DBDFF8042B15CD0BE6DE4461E0A" box="[434,576,877,891]" gridcol="2" gridrow="28" pageId="7" pageNumber="8">soluble</td>
<td id="76B35DBDFF8042B15F03BE6DE4E91E0A" box="[609,751,877,891]" gridcol="3" gridrow="28" pageId="7" pageNumber="8">soluble</td>
</tr>
<tr id="356234C1FF8042B15D16BE84E4E91EE3" box="[116,751,900,914]" gridrow="29" pageId="7" pageNumber="8">
<th id="76B35DBDFF8042B15D16BE84E4E91EE3" box="[116,751,900,914]" colspan="4" colspanRight="3" gridcol="0" gridrow="29" pageId="7" pageNumber="8">soluble</th>
</tr>
<tr id="356234C1FF8042B15D16BE9AE4E91ED8" box="[116,751,922,937]" gridrow="30" pageId="7" pageNumber="8">
<th id="76B35DBDFF8042B15D16BE9AE6FF1ED8" box="[116,249,922,937]" gridcol="0" gridrow="30" pageId="7" pageNumber="8">Log S (SILICOS-</th>
<td id="76B35DBDFF8042B15C6DBE9AE78B1ED8" box="[271,397,922,937]" gridcol="1" gridrow="30" pageId="7" pageNumber="8">3.01, soluble</td>
<td id="76B35DBDFF8042B15CD0BE9AE4461ED8" box="[434,576,922,937]" gridcol="2" gridrow="30" pageId="7" pageNumber="8">3.82, soluble</td>
<td id="76B35DBDFF8042B15F03BE9AE4E91ED8" box="[609,751,922,937]" gridcol="3" gridrow="30" pageId="7" pageNumber="8">3.04, soluble</td>
</tr>
<tr id="356234C1FF8042B15D16BEB1E4E91ECE" box="[116,751,945,959]" gridrow="31" pageId="7" pageNumber="8" rowspan-1="1" rowspan-2="1" rowspan-3="1">
<th id="76B35DBDFF8042B15D16BEB1E6FF1ECE" box="[116,249,945,959]" gridcol="0" gridrow="31" pageId="7" pageNumber="8">IT)</th>
</tr>
<tr id="356234C1FF8042B15D16BEC8E4E91EA7" box="[116,751,968,982]" gridrow="32" pageId="7" pageNumber="8" rowspan-1="1" rowspan-2="1" rowspan-3="1">
<th id="76B35DBDFF8042B15D16BEC8E6FF1EA7" box="[116,249,968,982]" gridcol="0" gridrow="32" pageId="7" pageNumber="8">Drug-likeness</th>
</tr>
<tr id="356234C1FF8042B15D16BEDBE4E91E9C" box="[116,751,987,1005]" gridrow="33" pageId="7" pageNumber="8">
<th id="76B35DBDFF8042B15D16BEDBE6FF1E9C" box="[116,249,987,1005]" gridcol="0" gridrow="33" pageId="7" pageNumber="8">Lipinski d</th>
<td id="76B35DBDFF8042B15C6DBEDBE78B1E9C" box="[271,397,987,1005]" gridcol="1" gridrow="33" pageId="7" pageNumber="8">Yes; 0 violation</td>
<td id="76B35DBDFF8042B15CD0BEDBE4461E9C" box="[434,576,987,1005]" gridcol="2" gridrow="33" pageId="7" pageNumber="8">Yes; 1 violation:</td>
<td id="76B35DBDFF8042B15F03BEDBE4E91E9C" box="[609,751,987,1005]" gridcol="3" gridrow="33" pageId="7" pageNumber="8">Yes; 1 violation:</td>
</tr>
<tr id="356234C1FF8042B15D16BEF6E4E91975" box="[116,751,1014,1028]" gridrow="34" pageId="7" pageNumber="8" rowspan-0="1" rowspan-1="1">
<td id="76B35DBDFF8042B15CD0BEF6E4461975" box="[434,576,1014,1028]" gridcol="2" gridrow="34" pageId="7" pageNumber="8">
MW
<emphasis id="B926EA91FF80BD495CB4BEF6E7E51975" box="[470,483,1014,1028]" italics="true" pageId="7" pageNumber="8">&gt;</emphasis>
500
</td>
<td id="76B35DBDFF8042B15F03BEF6E4E91975" box="[609,751,1014,1028]" gridcol="3" gridrow="34" pageId="7" pageNumber="8">
MW
<emphasis id="B926EA91FF80BD495FE7BEF6E4941975" box="[645,658,1014,1028]" italics="true" pageId="7" pageNumber="8">&gt;</emphasis>
500
</td>
</tr>
<tr id="356234C1FF8042B15D16B909E4E9196A" box="[116,751,1033,1051]" gridrow="35" pageId="7" pageNumber="8">
<th id="76B35DBDFF8042B15D16B909E6FF196A" box="[116,249,1033,1051]" gridcol="0" gridrow="35" pageId="7" pageNumber="8">Ghose e</th>
<td id="76B35DBDFF8042B15C6DB909E78B196A" box="[271,397,1033,1051]" gridcol="1" gridrow="35" pageId="7" pageNumber="8">No; 2 violations:</td>
<td id="76B35DBDFF8042B15CD0B909E446196A" box="[434,576,1033,1051]" gridcol="2" gridrow="35" pageId="7" pageNumber="8">No; 3 violations:</td>
<td id="76B35DBDFF8042B15F03B909E4E9196A" box="[609,751,1033,1051]" gridcol="3" gridrow="35" pageId="7" pageNumber="8">No; 3 violations:</td>
</tr>
<tr id="356234C1FF8042B15D16B924E4E91943" box="[116,751,1060,1074]" gridrow="36" pageId="7" pageNumber="8" rowspan-0="1">
<td id="76B35DBDFF8042B15C6DB924E78B1943" box="[271,397,1060,1074]" gridcol="1" gridrow="36" pageId="7" pageNumber="8">
MR
<emphasis id="B926EA91FF80BD495C4CB924E73D1943" box="[302,315,1060,1074]" italics="true" pageId="7" pageNumber="8">&gt;</emphasis>
130,
</td>
<td id="76B35DBDFF8042B15CD0B924E4461943" box="[434,576,1060,1074]" gridcol="2" gridrow="36" pageId="7" pageNumber="8">
MW
<emphasis id="B926EA91FF80BD495CB4B924E7E51943" box="[470,483,1060,1074]" italics="true" pageId="7" pageNumber="8">&gt;</emphasis>
480, MR
<emphasis id="B926EA91FF80BD495F4CB924E43D1943" box="[558,571,1060,1074]" italics="true" pageId="7" pageNumber="8">&gt;</emphasis>
</td>
<td id="76B35DBDFF8042B15F03B924E4E91943" box="[609,751,1060,1074]" gridcol="3" gridrow="36" pageId="7" pageNumber="8">
MW
<emphasis id="B926EA91FF80BD495FE7B924E4941943" box="[645,658,1060,1074]" italics="true" pageId="7" pageNumber="8">&gt;</emphasis>
480, MR
<emphasis id="B926EA91FF80BD495FBFB924E4EC1943" box="[733,746,1060,1074]" italics="true" pageId="7" pageNumber="8">&gt;</emphasis>
</td>
</tr>
<tr id="356234C1FF8042B15D16B93BE4E91938" box="[116,751,1083,1097]" gridrow="37" pageId="7" pageNumber="8" rowspan-0="1">
<td id="76B35DBDFF8042B15C6DB93BE78B1938" box="[271,397,1083,1097]" gridcol="1" gridrow="37" pageId="7" pageNumber="8">
#atoms
<emphasis id="B926EA91FF80BD495C2AB93BE7531938" box="[328,341,1083,1097]" italics="true" pageId="7" pageNumber="8">&gt;</emphasis>
70
</td>
<td id="76B35DBDFF8042B15CD0B93BE4461938" box="[434,576,1083,1097]" gridcol="2" gridrow="37" pageId="7" pageNumber="8">
130, #atoms
<emphasis id="B926EA91FF80BD495F71B93BE4261938" box="[531,544,1083,1097]" italics="true" pageId="7" pageNumber="8">&gt;</emphasis>
70
</td>
<td id="76B35DBDFF8042B15F03B93BE4E91938" box="[609,751,1083,1097]" gridcol="3" gridrow="37" pageId="7" pageNumber="8">
130, #atoms
<emphasis id="B926EA91FF80BD495FA3B93BE4C81938" box="[705,718,1083,1097]" italics="true" pageId="7" pageNumber="8">&gt;</emphasis>
70
</td>
</tr>
<tr id="356234C1FF8042B15D16B94DE4E91911" box="[116,751,1101,1120]" gridrow="38" pageId="7" pageNumber="8">
<th id="76B35DBDFF8042B15D16B94DE6FF1911" box="[116,249,1101,1120]" gridcol="0" gridrow="38" pageId="7" pageNumber="8">Veber f</th>
<td id="76B35DBDFF8042B15C6DB94DE78B1911" box="[271,397,1101,1120]" gridcol="1" gridrow="38" pageId="7" pageNumber="8">Yes</td>
<td id="76B35DBDFF8042B15CD0B94DE4461911" box="[434,576,1101,1120]" gridcol="2" gridrow="38" pageId="7" pageNumber="8">Yes</td>
<td id="76B35DBDFF8042B15F03B94DE4E91911" box="[609,751,1101,1120]" gridcol="3" gridrow="38" pageId="7" pageNumber="8">Yes</td>
</tr>
<tr id="356234C1FF8042B15D16B968E4E91907" box="[116,751,1128,1142]" gridrow="39" pageId="7" pageNumber="8">
<th id="76B35DBDFF8042B15D16B968E6FF1907" box="[116,249,1128,1142]" gridcol="0" gridrow="39" pageId="7" pageNumber="8">Bioavailability</th>
<td id="76B35DBDFF8042B15C6DB968E78B1907" box="[271,397,1128,1142]" gridcol="1" gridrow="39" pageId="7" pageNumber="8">0.55</td>
<td id="76B35DBDFF8042B15CD0B968E4461907" box="[434,576,1128,1142]" gridcol="2" gridrow="39" pageId="7" pageNumber="8">0.55</td>
<td id="76B35DBDFF8042B15F03B968E4E91907" box="[609,751,1128,1142]" gridcol="3" gridrow="39" pageId="7" pageNumber="8">0.55</td>
</tr>
<tr id="356234C1FF8042B15D16B97FE4E919FC" box="[116,751,1151,1165]" gridrow="40" pageId="7" pageNumber="8" rowspan-1="1" rowspan-2="1" rowspan-3="1">
<th id="76B35DBDFF8042B15D16B97FE6FF19FC" box="[116,249,1151,1165]" gridcol="0" gridrow="40" pageId="7" pageNumber="8">score</th>
</tr>
<tr id="356234C1FF8042B15D16B996E4E919D5" box="[116,751,1174,1188]" gridrow="41" pageId="7" pageNumber="8" rowspan-1="1" rowspan-2="1" rowspan-3="1">
<th id="76B35DBDFF8042B15D16B996E6FF19D5" box="[116,249,1174,1188]" gridcol="0" gridrow="41" pageId="7" pageNumber="8">Pharmacokinetics</th>
</tr>
<tr id="356234C1FF8042B15D16B9A9E4E919CD" box="[116,751,1193,1212]" gridrow="42" pageId="7" pageNumber="8">
<th id="76B35DBDFF8042B15D16B9A9E6FF19CD" box="[116,249,1193,1212]" gridcol="0" gridrow="42" pageId="7" pageNumber="8">Log Kg (skin p</th>
<td id="76B35DBDFF8042B15C6DB9A9E78B19CD" box="[271,397,1193,1212]" gridcol="1" gridrow="42" pageId="7" pageNumber="8">6.51 cm/s</td>
<td id="76B35DBDFF8042B15CD0B9A9E44619CD" box="[434,576,1193,1212]" gridcol="2" gridrow="42" pageId="7" pageNumber="8">6.56 cm/s</td>
<td id="76B35DBDFF8042B15F03B9A9E4E919CD" box="[609,751,1193,1212]" gridcol="3" gridrow="42" pageId="7" pageNumber="8">7.25 cm/s</td>
</tr>
<tr id="356234C1FF8042B15D16B9C4E4E919A3" box="[116,751,1220,1234]" gridrow="43" pageId="7" pageNumber="8" rowspan-1="1" rowspan-2="1" rowspan-3="1">
<th id="76B35DBDFF8042B15D16B9C4E6FF19A3" box="[116,249,1220,1234]" gridcol="0" gridrow="43" pageId="7" pageNumber="8">permeation)</th>
</tr>
</table>
</paragraph>
<tableNote id="76B4370DFF80BD495D11B9E3E7D618B5" pageId="7" pageNumber="8" targetBox="[116,751,213,1234]" targetPageId="7">
<paragraph id="8BED3683FF80BD495D11B9E3E7D51989" blockId="7.[100,770,1251,1479]" box="[115,467,1251,1272]" pageId="7" pageNumber="8">
<superScript id="7C279BCBFF80BD495D11B9E3E67C199E" attach="left" box="[115,122,1251,1263]" fontSize="5" pageId="7" pageNumber="8">a</superScript>
TPSA = Topological polar surface area.
</paragraph>
<paragraph id="8BED3683FF80BD495D11B9FCE4BF1860" blockId="7.[100,770,1251,1479]" box="[115,697,1276,1298]" pageId="7" pageNumber="8">
<superScript id="7C279BCBFF80BD495D11B9FCE67D1879" attach="left" box="[115,123,1276,1288]" fontSize="5" pageId="7" pageNumber="8">b</superScript>
Log P= The partition coefficient between n-octanol and water.
</paragraph>
<paragraph id="8BED3683FF80BD495DD6B808E4A5185A" blockId="7.[100,770,1251,1479]" pageId="7" pageNumber="8">
<subScript id="17D634C6FF80BD495DD6B808E6C81865" attach="left" box="[180,206,1288,1300]" fontSize="5" pageId="7" pageNumber="8">o/w</subScript>
<superScript id="7C279BCBFF80BD495D11B816E67C1853" attach="left" box="[115,122,1302,1314]" fontSize="5" pageId="7" pageNumber="8">c</superScript>
Log S = The decimal logarithm of the molar solubility in water.
</paragraph>
<paragraph id="8BED3683FF80BD495D11B82FE7BE182E" blockId="7.[100,770,1251,1479]" pageId="7" pageNumber="8">
<superScript id="7C279BCBFF80BD495D11B82FE67D184A" attach="right" box="[115,123,1327,1339]" fontSize="5" pageId="7" pageNumber="8">d</superScript>
Lipinski criteria range are, lipophilicity (Log P) ≤ 5, MW ≤ 500, H-bond 
<subScript id="17D634C6FF80BD495F6EB83BE4231836" attach="left" box="[524,549,1339,1351]" fontSize="5" pageId="7" pageNumber="8">o/w</subScript>
donors ≤ 5 and H-bond acceptors ≤ 10.
</paragraph>
<paragraph id="8BED3683FF80BD495D11B862E43A18E0" blockId="7.[100,770,1251,1479]" pageId="7" pageNumber="8">
<superScript id="7C279BCBFF80BD495D11B862E67C181F" attach="right" box="[115,122,1378,1390]" fontSize="5" pageId="7" pageNumber="8">e</superScript>
Ghose filter criteria range are, Log Pin 0.4 to +5.6 range, MR from 40 to 
<subScript id="17D634C6FF80BD495CCCB86EE7CE180B" attach="left" box="[430,456,1390,1402]" fontSize="5" pageId="7" pageNumber="8">o/w</subScript>
130, MW from 180 to 480, No. of atoms from 20 to 70.
</paragraph>
<paragraph id="8BED3683FF80BD495D11B895E47418DB" blockId="7.[100,770,1251,1479]" box="[115,626,1429,1451]" pageId="7" pageNumber="8">
<superScript id="7C279BCBFF80BD495D11B895E67E18D0" attach="left" box="[115,120,1429,1441]" fontSize="5" pageId="7" pageNumber="8">f</superScript>
Veber rule criteria range are, RB ≤ 10 and TPSA ≤140 Å 
<superScript id="7C279BCBFF80BD495F07B895E46B18D0" attach="left" box="[613,621,1429,1441]" fontSize="5" pageId="7" pageNumber="8">2</superScript>
.
</paragraph>
<paragraph id="8BED3683FF80BD495D11B8AFE7D618B5" blockId="7.[100,770,1251,1479]" box="[115,464,1455,1476]" pageId="7" pageNumber="8">
<superScript id="7C279BCBFF80BD495D11B8AFE67D18CA" attach="left" box="[115,123,1455,1467]" fontSize="5" pageId="7" pageNumber="8">g</superScript>
Log K= skin permeability coefficient.
</paragraph>
</tableNote>
<paragraph id="8BED3683FF80BD495DD7B8BBE6BB18B6" blockId="7.[100,770,1251,1479]" box="[181,189,1467,1479]" pageId="7" pageNumber="8">
<subScript id="17D634C6FF80BD495DD7B8BBE6BB18B6" attach="left" box="[181,189,1467,1479]" fontSize="5" pageId="7" pageNumber="8">p</subScript>
</paragraph>
<paragraph id="8BED3683FF80BD495D06BA3BE6CC1A18" blockId="7.[100,754,1851,1898]" pageId="7" pageNumber="8">
<heading id="D0A581EFFF80BD495D06BA3BE6CC1A18" bold="true" centered="true" fontSize="36" level="1" pageId="7" pageNumber="8" reason="1">
<emphasis id="B926EA91FF80BD495D06BA3BE4F41A3F" bold="true" box="[100,754,1851,1870]" italics="true" pageId="7" pageNumber="8">2.8. In silico molecular modeling analysis of conoidecyclics isolated from</emphasis>
<taxonomicName id="4C524D00FF80BD495D06BA57E6CC1A18" box="[100,202,1878,1898]" class="Anthozoa" family="Dendrophylliidae" genus="Turbinaria" kingdom="Animalia" order="Scleractinia" pageId="7" pageNumber="8" phylum="Cnidaria" rank="species" species="conoides">
<emphasis id="B926EA91FF80BD495D06BA57E6CC1A18" bold="true" box="[100,202,1878,1898]" italics="true" pageId="7" pageNumber="8">T. conoides</emphasis>
</taxonomicName>
</heading>
</paragraph>
<paragraph id="8BED3683FF80BD495DE6BA8FE2201FC8" blockId="7.[100,770,1935,1982]" lastBlockId="7.[818,1488,148,697]" pageId="7" pageNumber="8">
The macrocyclic derivatives (conoidecyclics A-C) were subjected to in-silico molecular modeling studies against pro-inflammatory 5- 
<collectionCode id="ED43AE46FF80BD495FB7BAAAE5041ACC" box="[725,770,1962,1981]" pageId="7" pageNumber="8">LOX</collectionCode>
and COX-2 enzymes, and the results were obtained with the help of RMSD data. Conoidecyclic A, on molecular modeling with COX-2 and ACE-I exhibited three hydrogen bonding interactions with the enzyme active site, whereas five hydrogen bonds were apparent between the ligand and the active site amino acyl residues of PTP-1B (
<figureCitation id="13692A06FF80BD49585DBC03E3741C67" box="[1343,1394,259,278]" captionStart="Fig" captionStartId="8.[100,130,625,642]" captionTargetBox="[115,1474,151,596]" captionTargetId="figure-459@8.[112,1476,148,597]" captionTargetPageId="8" captionText="Fig. 3. (A1-A2) Representative hydrogen binding interactions between conoidecyclic A and the amino acyl residues in the catalytic sites of COX-2; (A3-A4) Representative hydrogen binding interactions between conoidecyclic A and the amino acyl residues in the catalytic sites of 5-LOX; (A5-A6) Representative hydrogen binding interactions between conoidecyclic A and the amino acyl residues in the catalytic sites of PTP-1B; (A7-A8) Representative hydrogen binding interactions between conoidecyclic A and the amino acyl residues in the catalytic sites of ACE as obtained from in silico molecular docking analysis." figureDoi="http://doi.org/10.5281/zenodo.8258126" httpUri="https://zenodo.org/record/8258126/files/figure.png" pageId="7" pageNumber="8">Fig. 3</figureCitation>
, 
<tableCitation id="C6D00338FF80BD49581FBC03E3C71C67" box="[1405,1473,259,278]" captionStart="Table 4" captionStartId="11.[100,150,150,166]" captionTargetPageId="11" captionText="Table 4 In silico molecular docking parameters between the ligands (conoidecyclics A-C) and the amino acyl residues at the active sites of COX-2, 5-LOX, PTP-1B and ACE." pageId="7" pageNumber="8">Table 4</tableCitation>
). In comparison, conoidecyclic B and C exhibited lesser number of hydrogen bonding interactions with the active site of targeted enzymes (
<figureCitation id="13692A06FF80BD495E58BC57E5961C1B" box="[826,912,343,362]" captionStart-0="Fig" captionStart-1="Fig" captionStartId-0="8.[100,130,1258,1275]" captionStartId-1="9.[100,130,723,740]" captionTargetBox-0="[114,1472,777,1230]" captionTargetBox-1="[113,1473,149,692]" captionTargetId-0="figure-549@8.[112,1474,775,1231]" captionTargetId-1="figure-1028@9.[112,1475,148,695]" captionTargetPageId-0="8" captionTargetPageId-1="9" captionText-0="Fig. 4. (A1-A2) Representative hydrogen binding interactions between conoidecyclic B and the amino acyl residues in the catalytic sites of COX-2; (A3-A4) Representative hydrogen binding interactions between conoidecyclic B and the amino acyl residues in the catalytic sites of 5-LOX; (A5-A6) Representative hydrogen binding interactions between conoidecyclic B and the amino acyl residues in the catalytic sites of PTP-1B; (A7-A8) Representative hydrogen binding interactions between conoidecyclic B and the amino acyl residues in the catalytic sites of ACE as obtained from in silico molecular docking analysis." captionText-1="Fig. 5. (A1-A2) Representative hydrogen binding interactions between conoidecyclic C and the amino acyl residues in the catalytic sites of COX-2; (A3-A4) Representative hydrogen binding interactions between conoidecyclic C and the amino acyl residues in the catalytic sites of 5-LOX; (A5-A6) Representative hydrogen binding interactions between conoidecyclic C and the amino acyl residues in the catalytic sites of PTP-1B; (A7-A8) Representative hydrogen binding interactions between conoidecyclic C and the amino acyl residues in the catalytic sites of ACE as obtained from in silico molecular docking analysis." figureDoi-0="http://doi.org/10.5281/zenodo.8258128" figureDoi-1="http://doi.org/10.5281/zenodo.8258130" httpUri-0="https://zenodo.org/record/8258128/files/figure.png" httpUri-1="https://zenodo.org/record/8258130/files/figure.png" pageId="7" pageNumber="8">Figs. 4–5</figureCitation>
, 
<tableCitation id="C6D00338FF80BD495EFCBC57E5E01C1B" box="[926,998,343,362]" captionStart="Table 4" captionStartId="11.[100,150,150,166]" captionTargetPageId="11" captionText="Table 4 In silico molecular docking parameters between the ligands (conoidecyclics A-C) and the amino acyl residues at the active sites of COX-2, 5-LOX, PTP-1B and ACE." pageId="7" pageNumber="8">Table 4</tableCitation>
). Likewise, conoidecyclic A recorded least binding energy (13.34, 14.51, 13.87 and 11.27 kcal mol 
<superScript id="7C279BCBFF80BD49582EBC6DE3531C0A" attach="right" box="[1356,1365,365,379]" fontSize="6" pageId="7" pageNumber="8">1</superScript>
with 5- 
<collectionCode id="ED43AE46FF80BD4958FFBC73E3CA1CF7" box="[1437,1484,371,390]" pageId="7" pageNumber="8">LOX</collectionCode>
, COX-2, PTP-1B and ACE-I respectively) and docking score (~ 12 to 15 kcal mol 
<superScript id="7C279BCBFF80BD495EABBCA5E5D41CC2" attach="right" box="[969,978,421,435]" fontSize="6" pageId="7" pageNumber="8">1</superScript>
) than those displayed by conoidecyclics B and C (
<tableCitation id="C6D00338FF80BD495E58BCC7E5841CAB" box="[826,898,455,474]" captionStart="Table 4" captionStartId="11.[100,150,150,166]" captionTargetPageId="11" captionText="Table 4 In silico molecular docking parameters between the ligands (conoidecyclics A-C) and the amino acyl residues at the active sites of COX-2, 5-LOX, PTP-1B and ACE." pageId="7" pageNumber="8">Table 4</tableCitation>
). Likewise, the constant of enzyme inhibition, 
<subScript id="17D634C6FF80BD495828BCC7E35A1CAD" attach="left" box="[1354,1372,455,476]" fontSize="6" pageId="7" pageNumber="8">Ki</subScript>
upon interaction with COX-2 and 5- 
<collectionCode id="ED43AE46FF80BD495975BCE2E2421C84" box="[1047,1092,482,501]" pageId="7" pageNumber="8">LOX</collectionCode>
were lesser for conoidecyclic A (23.20 and 33.23 pM, respectively) followed by those of conoidecyclic B and C (
<tableCitation id="C6D00338FF80BD495E58BF1AE5871F5C" box="[826,897,538,557]" captionStart="Table 4" captionStartId="11.[100,150,150,166]" captionTargetPageId="11" captionText="Table 4 In silico molecular docking parameters between the ligands (conoidecyclics A-C) and the amino acyl residues at the active sites of COX-2, 5-LOX, PTP-1B and ACE." pageId="7" pageNumber="8">Table 4</tableCitation>
). The lowest docking score as well as binding energy of conoidecyclic A described its greater attenuation potential against 5- 
<collectionCode id="ED43AE46FF80BD4958C0BF36E3C91F38" box="[1442,1487,566,585]" pageId="7" pageNumber="8">LOX</collectionCode>
and COX-2 enzymes, which were reported to produce inflammatory prostaglandins (PGE 
<subScript id="17D634C6FF80BD495E93BF75E5FC1FF2" attach="left" box="[1009,1018,629,643]" fontSize="6" pageId="7" pageNumber="8">2</subScript>
, PGG 
<subScript id="17D634C6FF80BD495952BF75E23F1FF2" attach="left" box="[1072,1081,629,643]" fontSize="6" pageId="7" pageNumber="8">2</subScript>
, PGI 
<subScript id="17D634C6FF80BD495905BF75E2761FF2" attach="left" box="[1127,1136,629,643]" fontSize="6" pageId="7" pageNumber="8">2</subScript>
, PGF 
<subScript id="17D634C6FF80BD4959C1BF75E2AA1FF2" attach="left" box="[1187,1196,629,643]" fontSize="6" pageId="7" pageNumber="8">2</subScript>
etc), thromboxane (TXA 
<subScript id="17D634C6FF80BD4958F7BF75E3981FF2" attach="left" box="[1429,1438,629,643]" fontSize="6" pageId="7" pageNumber="8">2</subScript>
) and leukotrienes (such as LTB 
<subScript id="17D634C6FF80BD495945BF91E2361FEE" attach="left" box="[1063,1072,657,671]" fontSize="6" pageId="7" pageNumber="8">4</subScript>
) causing the development of inflammation (
<bibRefCitation id="EFC34B72FF80BD495E58BFA6E21F1FC8" author="Hanna, V. S. &amp; Hafez, E. A. A." box="[826,1049,678,697]" pageId="7" pageNumber="8" pagination="23 - 32" refId="ref15366" refString="Hanna, V. S., Hafez, E. A. A., 2018. Synopsis of arachidonic acid metabolism: a review. J. Adv. Res. 11, 23 - 32. https: // doi. org / 10.1016 / j. jare. 2018.03.005." type="journal article" year="2018">Hanna and Hafez, 2018</bibRefCitation>
).
</paragraph>
</subSubSection>
</treatment>
</document>