Design, synthesis and MAO inhibitory activity of 2-(arylmethylidene)2,3-dihydro-l-benzofuran-3-one derivatives


Badavath V. N., Nath C., Ganta N. M., UÇAR G., Sinha B. N., Jayaprakash V.

CHINESE CHEMICAL LETTERS, vol.28, no.7, pp.1528-1532, 2017 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 28 Issue: 7
  • Publication Date: 2017
  • Doi Number: 10.1016/j.cclet.2017.02.009
  • Journal Name: CHINESE CHEMICAL LETTERS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1528-1532
  • Hacettepe University Affiliated: Yes

Abstract

A series of 2-(arylmethylidene)-2,3-dihydro-1-benzofuran-3-one derivatives (aurones, 1-20) were synthesized and screened for their inhibitory activity against hMAO. Seventeen compounds (1-5, 7-17, 19) were found to be selective towards hMAO-B, while two were non -selective (6 and 20) and one (18) selective towards hMAO-A. Compound 17 (Ki = 0.10 +/- 0.01 mu mol/L) was found to be equally potent and selective towards hMAO-B, when compared with the standard drug Selegiline (Ki = 0.12 0.01 p.mol/L). Nature and position of substitution in aryl ring at 2nd position of benzofuranone influences hMAO-B inhibitory potency, while their structural bulkiness influences selectivity between hMAO-A and hMAO-B. Molecular docking simulation was also carried out to understand the interaction of inhibitor with the enzyme at molecular level, and we found the docking results were in good agreement with the experimental values. Comparison of the activity profile of the aurones with their corresponding flavones reported earlier by our group revealed that there exists no difference in potency as well as selectivity. (C) 2017 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.