Monoamine Oxidase Inhibitory Activity of Ferulic Acid Amides: Curcumin-Based Design and Synthesis

Published in: Journal, Article, Research Support, Non-U.S. Gov’t Volume : 349, Issue : 1, Pages : 9-19

DOI : 10.1002/ardp.201500317

Author : Badavath, Vishnu N.; Baysal, Ipek; Ucar, Guelberk; Mondal, Susanta K.; Sinha, Barij N.; Jayaprakash, Venkatesan

Abstract : Ferulic acid has structural similarity with curcumin which is being reported for its monoamine oxidase (MAO) inhibitory activity. Based on this similarity, the authors designed a series of ferulic acid amides and tested for their inhibitory activity on human MAO (hMAO) isoforms. All the compounds were found to inhibit the hMAO isoforms either selectively or nonselectively. Nine compounds were found to inhibit hMAO-B selectively, whereas the other four were found to be nonselective. There is a gradual shift from hMAO-B selectivity to nonselectivity as there is an increase in chain length at the amino terminus. In case of compounds having an aromatic nucleus at the amino terminus, increasing the carbon number between N and the aromatic ring increases the potency as well as selectivity toward hMAO-B. Three compounds were subjected to membrane permeability and metabolic stability studies by in vitro assay methods. They were found to have a better pharmacokinetic profile than curcumin, ferulic acid, and selegiline. In order to understand the structural features responsible for the potency and selectivity of I, the authors carried out a mol. docking simulation study.