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ARS Home » Southeast Area » Oxford, Mississippi » Natural Products Utilization Research » Research » Publications at this Location » Publication #378613

Research Project: Biobased Pesticide Discovery and Product Optimization and Enhancement from Medicinal and Aromatic Crops

Location: Natural Products Utilization Research

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

item ELIWA, DUAA - University Of Mississippi
item ALBADRY, MOHAMED - University Of Mississippi
item IBRAHIM, ABDEL-RAHIM - Tanta University
item KABBASH, AMAL - Tanta University
item Meepagala, Kumudini
item KHAN, IKHLAS - University Of Mississippi
item EL-AASR, MONA - Tanta University
item ROSS, SAMIR - University Of Mississippi

Submitted to: Phytochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/24/2020
Publication Date: 12/25/2020
Citation: Eliwa, D., Albadry, M.A., Ibrahim, A.S., Kabbash, A., Meepagala, K.M., Khan, I.A., El-Aasr, M., Ross, S.A. 2020. Biotransformation of papaverine and in silico docking studies of the metabolites on human phosphodiesterase 10a.. Phytochemistry.

Interpretive Summary: Benzylisoquinoline alkaloids are antimicrobial compounds that have been shown to possess antifungal activities against plant and animal pathogens. Microbial transformation (biotransformations (bioconversion or microbial transformation)) refer to the processes in which microorganisms convert organic compounds into structurally related products that cannot be easily synthesized in laboratory settings that can possess enhanced biological activities. In this paper we describe the biotransformation of papaverine using various fungal strains.

Technical Abstract: 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-ß-d-glucopyranosyl) 4'-demethyl papaverine and (4''-O-methyl-ß-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.