Biotransformation of papaverine and in silico docking studies of the metabolites on human phosphodiesterase 10a.

Autor: Eliwa D; 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., Albadry MA; National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, MS, 38677, USA., Ibrahim AS; Department of Pharmacognosy, Faculty of Pharmacy, Tanta University, Tanta, 31527, Egypt., Kabbash A; Department of Pharmacognosy, Faculty of Pharmacy, Tanta University, Tanta, 31527, Egypt., Meepagala K; USDA-ARS, Natural Products Utilization Research Unit, University, MS, USA., Khan IA; 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., El-Aasr M; Department of Pharmacognosy, Faculty of Pharmacy, Tanta University, Tanta, 31527, Egypt., Ross SA; 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. Electronic address: sross@olemiss.edu.
Jazyk: angličtina
Zdroj: Phytochemistry [Phytochemistry] 2021 Mar; Vol. 183, pp. 112598. Date of Electronic Publication: 2020 Dec 25.
DOI: 10.1016/j.phytochem.2020.112598
Abstrakt: The metabolism of papaverine, the opium benzylisoquinoline alkaloid, with Aspergillus niger NRRL 322, Beauveria bassiana NRRL 22864, Cunninghamella echinulate ATCC 18968 and Cunninghamella echinulate ATCC 1382 has resulted in O-demethylation, O-methylglucosylation and N-oxidation products. Two new metabolites (4″-O-methyl-β-D-glucopyranosyl) 4'-demethyl papaverine and (4″-O-methyl-β-D-glucopyranosyl) 6-demethyl papaverine, (Metabolites 5 and 6) together with 4'-O-demethylated papaverine (Metabolite 1), 3'-O-demethylated papaverine (Metabolite 2), 6-O-demethylated papaverine (Metabolite 3) and papaverine N-oxide (Metabolite 4) were isolated. The structure elucidation of the metabolites was based primarily on 1D, 2D-NMR analyses and HRMS. These metabolism results were consistent with the previous plant cell transformation studies on papaverine and isopapaverine and the microbial metabolism of papaveraldine. In silico docking studies of the metabolites using crystals of human phosphodiesterase 10a (hPDE10a) revealed that compounds 4, 1, 6, 3, and 5 possess better docking scores and binding poses with favorable interactions than the native ligand papaverine.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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