Microbial transformation of some simple isoquinoline and benzylisoquinoline alkaloids and in vitro studies of their metabolites

Mona El-Aasr; Duaa Eliwa; Mohamed Albadry; Abdel-Rahim S Ibrahim; Amal Kabbash; Kumudini M Meepagala; Ikhlas A Khan; Shabana I Khan; Samir A Ross

doi:10.1016/j.phytochem.2021.112828

Microbial transformation of some simple isoquinoline and benzylisoquinoline alkaloids and in vitro studies of their metabolites

Phytochemistry. 2021 Sep:189:112828. doi: 10.1016/j.phytochem.2021.112828. Epub 2021 Jun 24.

Authors

Mona El-Aasr¹, Duaa Eliwa², Mohamed Albadry³, Abdel-Rahim S Ibrahim¹, Amal Kabbash¹, Kumudini M Meepagala⁴, Ikhlas A Khan³, Shabana I Khan³, Samir A Ross⁵

Affiliations

¹ Department of Pharmacognosy, Faculty of Pharmacy, Tanta University, Tanta, 31527, Egypt.
² Department of Pharmacognosy, Faculty of Pharmacy, Tanta University, Tanta, 31527, Egypt; National Center of Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677, USA.
³ National Center of Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677, USA; Division of Pharmacognosy, Department of Biomolecular Sciences, School of Pharmacy, University of Mississippi, MS, 38677, USA.
⁴ USDA-ARS, Natural Products Utilization Research Unit, University, MS, USA.
⁵ National Center of Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677, USA; Division of Pharmacognosy, Department of Biomolecular Sciences, School of Pharmacy, University of Mississippi, MS, 38677, USA. Electronic address: sross@olemiss.edu.

PMID: 34174637
DOI: 10.1016/j.phytochem.2021.112828

Abstract

Simple isoquinoline alkaloids (heliamine, dehydroheliamine), a phthalide isoquinoline alkaloid noscapine, and an aporphine alkaloid boldine are biosynthetically derived from an amino acid tyrosine. These substrates and a simple synthetic isoquinoline alkaloid (2-acetyl-7-amino-1,2,3,4-tetrahydroisoquinoline) contain an isoquinoline nucleus. The biotransformation of these substrates via reduction, oxidation, hydroxylation, and N-oxidation reactions with different microorganism produced nine metabolites, namely: 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). Primarily, the metabolites are structurally elucidated by one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) analyses, and high-resolution electrospray ionization mass spectrometry (HR-ESIMS). Furthermore, the substrates and their isolated metabolites are evaluated in vitro for their anti-inflammatory, antimicrobial, cytotoxicity, and anticancer activities. The in vitro studies reveal that some of the isolated compounds are potential as anti-inflammatory, antitumor, and antimicrobial leads.

Keywords: Isoquinoline alkaloids; Microbial transformation; iNOS.

MeSH terms

Alkaloids* / pharmacology
Benzylisoquinolines* / pharmacology
Isoquinolines / pharmacology
Molecular Structure
Spectrometry, Mass, Electrospray Ionization

Substances

Alkaloids
Benzylisoquinolines
Isoquinolines