Coumarin-Resveratrol-Inspired Hybrids As Monoamine Oxidase B Inhibitors: 3-Phenylcoumarin  -6-Styrylcoumarin

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2022 Feb 15

PMID 35164192

Authors

Marco Mellado

Cesar Gonzalez

Jaime Mella

Luis F Aguilar

Ismail Celik

Fernanda Borges

Eugenio Uriarte

Giovanna Delogu

Dolores Vina

Maria J Matos

Affiliations

Soon will be listed here.

Abstract

Monoamine oxidases (MAOs) are attractive targets in drug design. The inhibition of one of the isoforms (A or B) is responsible for modulating the levels of different neurotransmitters in the central nervous system, as well as the production of reactive oxygen species. Molecules that act selectively on one of the MAO isoforms have been studied deeply, and coumarin has been described as a promising scaffold. In the current manuscript we describe a comparative study between 3-phenylcoumarin ( coumarin-resveratrol-inspired hybrid) and -6-styrylcoumarin ( coumarin-resveratrol-inspired hybrid). Crystallographic structures of both compounds were obtained and analyzed. 3D-QSAR models, in particular CoMFA and CoMSIA, docking simulations and molecular dynamics simulations have been performed to support and better understand the interaction of these molecules with both MAO isoforms. Both molecules proved to inhibit MAO-B, with -6-styrylcoumarin being 107 times more active than 3-phenylcoumarin, and 267 times more active than -resveratrol.

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Coumarin-Resveratrol-Inspired Hybrids As Monoamine Oxidase B Inhibitors: 3-Phenylcoumarin &nbsp;-6-Styrylcoumarin

Coumarin-Resveratrol-Inspired Hybrids As Monoamine Oxidase B Inhibitors: 3-Phenylcoumarin -6-Styrylcoumarin