Design, synthesis and biological evaluation of novel benzocoumarin derivatives as potent inhibitors of MAO-B activity


MELETLİ F., Gündüz C., Alparslan M. M., ATTAR A., DEMİR S., İskit E., ...More

Bioorganic and Medicinal Chemistry Letters, vol.113, 2024 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 113
  • Publication Date: 2024
  • Doi Number: 10.1016/j.bmcl.2024.129984
  • Journal Name: Bioorganic and Medicinal Chemistry Letters
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, MEDLINE, Veterinary Science Database
  • Keywords: Benzo[g]coumarin, Benzo[h]coumarin, Molecular docking, Monoamine oxidase, Parkinson's Disease
  • Yıldız Technical University Affiliated: Yes

Abstract

The continued research of novel reversible inhibitors targeting monoamine oxidase (MAO) B remains crucial for effectively symptomatic treatment of Parkinson's disease. In this study we synthesized and evaluated a new series of 3-aryl benzo[g] and benzo[h] coumarin derivatives as MAO-B inhibitors. Compound A6 has been found to display the most potent inhibitory activity and selectivity against the MAO-B isoform (IC50 = 13 nM and SI = >7693.31 respectively). Inhibition mode of A6 on MAO-B was predicted as mixed reversible inhibition with a Ki value of 3.274 nM. Furthermore, in order to elaborate structure–activity relationships, the binding mode of A6 was investigated by molecular docking simulations.