Microbial transformation of some simple isoquinoline and benzyl isoquinoline alkaloids and molecular docking studies of the metabolites

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

Submitted to: Phytochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/31/2021
Publication Date: 6/24/2021
Citation: El-Aasr, M., Eliwa, D., Albadry, M.A., Ibrahim, A.S., Kabbash, A., Meepagala, K.M., Khan, I.A., Ross, S.A., Khan, S.I. 2021. Microbial transformation of some simple isoquinoline and benzyl isoquinoline alkaloids and molecular docking studies of the metabolites. Phytochemistry. https://doi.org/10.1016/j.phytochem.2021.112828.
DOI: https://doi.org/10.1016/j.phytochem.2021.112828

Interpretive Summary: Biotransformation is a process by which organic compounds are transformed from one form to another to reduce the persistence and toxicity of the chemical compounds. This process is aided by many microorganisms and their products such as bacteria, fungi and enzymes. Biotransformation can also be used to facilitate the synthesis of compounds or materials, if synthetic approaches are challenging. Isoquinoline alkaloids are widely distributed in many sections of plants and they also have anti-inflammatory, analgesic, spasmolysis, antibacterial, and relieving asthma effects. Twenty-five strains of filamentous fungi of different classes were used in the initial screening of isoquinoline alkaloid substrates (heliamine, dehydroheliamine, 2-acetyl-7-amino1,2,3,4-tetrahydroisoquinoline, noscapine and boldine). Nine metabolites were isolated from the biotransformation broth and freeze–dried mycelia of Aspergillus niger NRRL 322, Beauveria bassiana NRRL 22864, Cunninghamella echinulate ATCC 18968, Penicillium roqueforti NRRL 849, Mucor plumbeus NRRL 2630 and Cunninghamella echinulate ATCC 1382. The metabolites were identified on the basis of their mass and NMR spectroscopic data.

Technical Abstract: Simple isoquinoline alkaloids (heliamine, dehydroheliamine), the phthalide isoquinoline alkaloid noscapine and aporphine alkaloid boldine are biosynthetically derived from amino acid tyrosine and the synthetic simple isoquinoline alkaloid 2-acetyl-7-amino1,2,3,4-tetrahydroisoquinoline, all contain isoquinoline nucleus. The biotransformation of these substrates with different microorganism produced ten metabolites via reduction, oxidation, hydroxylation and N-oxidation reactions. The metabolites included: N-(2-acetyl-1,2,3,4-tetrahydroisoquinolin-7-yl) acetamide (metabolite-1), heliamine N-oxide (metabolite-2), 6,7-dimethoxyisoquinoline (metabolite-3), 3, 4-dihydro-6, 7-dimethoxy isoquinolin-1-one (metabolite-4), heliamine (metabolite-5), dehydroheliamine N-oxide (metabolite-6), cotarnine (metabolite-7), 5-hydroxy cotarnine (metabolite-8) and boldine N-oxide (metabolite-9). The structural elucidation of the metabolites was based primarily on 1D, 2D-NMR analyses and HR-ESIMS. Furthermore, exploration of the substrates and their isolated metabolites as inhibitors of inflammation-related molecular targets, molecular docking studies targeting Human adipocyte lipid-binding protein FABP4 (3P6H) and Human Nitric oxide synthase (3E7G) were carried out. Furthermore, the in vitro evaluation of the substrates and their isolated metabolites for their anti-inflammatory and anti-microbial activities was investigated. The in silico and in vitro studies indicated that some of the isolated compounds hold potentials as anti-inflammatory, and antimicrobial leads.