Back to Journals » Drug Design, Development and Therapy » Volume 9

3-Coumaranone derivatives as inhibitors of monoamine oxidase

Authors Van Dyk A, Petzer J, Petzer A, Legoabe L

Received 5 June 2015

Accepted for publication 28 July 2015

Published 3 October 2015 Volume 2015:9 Pages 5479—5489

DOI https://doi.org/10.2147/DDDT.S89961

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Venkateshwar Madka

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Wei Duan


Adriaan S Van Dyk,1,2 Jacobus P Petzer,1,2 Anél Petzer,1 Lesetja J Legoabe1

1Centre of Excellence for Pharmaceutical Sciences, 2Pharmaceutical Chemistry, School of Pharmacy, North-West University, Potchefstroom, South Africa

Abstract: The present study examines the monoamine oxidase (MAO) inhibitory properties of a series of 20 3-coumaranone [benzofuran-3(2H)-one] derivatives. The 3-coumaranone derivatives are structurally related to series of α-tetralone and 1-indanone derivatives, which have recently been shown to potently inhibit MAO, with selectivity for MAO-B (in preference to the MAO-A isoform). 3-Coumaranones are similarly found to selectively inhibit human MAO-B with half-maximal inhibitory concentration (IC50) values of 0.004–1.05 µM. Nine compounds exhibited IC50<0.05 µM for the inhibition of MAO-B. For the inhibition of human MAO-A, IC50 values ranged from 0.586 to >100 µM, with only one compound possessing an IC50<1 µM. For selected 3-coumaranone derivatives, it is established that MAO-A and MAO-B inhibition are reversible since dialysis of enzyme–inhibitor mixtures almost completely restores enzyme activity. On the basis of the selectivity profiles and potent action, it may be concluded that the 3-coumaranone derivatives are suitable leads for the development of selective MAO-B inhibitors as potential treatment for disorders such as Parkinson’s disease and Alzheimer’s disease.

Keywords: benzofuran-3(2H)-one, MAO, inhibition, reversible, competitive, Parkinson’s disease
 

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]