Biotransformation of papaverine and in silico docking studies of the metabolites on human phosphodiesterase 10 a Author Eliwa, Duaa * & National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, MS, 38677, USA & Department of Pharmacognosy, Faculty of Pharmacy, Tanta University, Tanta, 31527, Egypt Author Albadry, Mohamed A. * & National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, MS, 38677, USA Author Ibrahim, Abdel-Rahim S. Department of Pharmacognosy, Faculty of Pharmacy, Tanta University, Tanta, 31527, Egypt Author Kabbash, Amal Department of Pharmacognosy, Faculty of Pharmacy, Tanta University, Tanta, 31527, Egypt Author Meepagala, Kumudini USDA-ARS, Natural Products Utilization Research Unit, University, MS, USA Author Khan, Ikhlas A. * & National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, MS, 38677, USA & * & Division of Pharmacognosy, Department of Biomolecular Sciences, School of Pharmacy, University of Mississippi, MS, 38677, USA Author El-Aasr, Mona Department of Pharmacognosy, Faculty of Pharmacy, Tanta University, Tanta, 31527, Egypt Author Ross, Samir A. * & National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, MS, 38677, USA & * & Division of Pharmacognosy, Department of Biomolecular Sciences, School of Pharmacy, University of Mississippi, MS, 38677, USA text Phytochemistry 2021 112598 2021-03-31 183 1 12 http://dx.doi.org/10.1016/j.phytochem.2020.112598 journal article 264534 10.1016/j.phytochem.2020.112598 c3ebb44c-c81a-4b58-9d60-13c793e6db2b 1873-3700 8291902 3.5. Microbial transformation using Aspergillus niger NRRL 322 Biotransformation of papaverine using Aspergillus niger NRRL 322 afforded to two metabolites (2 and 3). The residue (1 gm) was dissolved in 50 ml of methanol/dichloromethane mixture (1:1) and adsorbed onto 1 gm Celite and dried. The adsorbed sample was placed onto a glass column (50 × 2.5 cm ) packed with silica after making a slurry in dichloromethane. The column was isocratically eluted with dichloromethane: methanol (97.5:2.5) and 10 ml fractions were collected. Fractions 20–44 were pooled together to give mixture of 2 and 3 as determined by TLC. The metabolites were obtained in the form of yellowish residue ( 80 mg , R f 0.3 S 2 ). ) continued ( 4 Table Fig. 2. Docked poses of the five papaverine-based biotransformation products with better docking scores than the native ligand in the Human PDE-10 A crystal structure, PDB: 2WEY; 4 (red), 1 (yellow), 6 (blue), 3 (blum), 5 (faded orange). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.) Fig. 3. Structure of papaverine and its metabolite from different Fungi. The mixture was loaded in silica biotage column (18 × 150 mm ). The column was gradiently eluted with dichloromethane 100% then dichloromethane:2-propanol (98:2, 97:3,95:5) and 20 ml fractions were collected. Fractions 27–31 were pooled together to give pure 2 , in the form of white powder ( 7 mg , Rf 0.70 S 1 ). Fractions 65–85 were pooled together to give pure 3 , in the form of white powder ( 30 mg , R f 0.61 S 1 ).