Synthesis,in vitroenzyme activity and molecular docking studies of new benzylamine-sulfonamide derivatives as selective MAO-B inhibitors

SAĞLIK B. N., OSMANİYE D., ACAR ÇEVİK U., LEVENT S., Kaya cavusoglu B., ATLI EKLİOĞLU Ö., ...More

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, vol.35, no.1, pp.1422-1432, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 35 Issue: 1
  • Publication Date: 2020
  • Doi Number: 10.1080/14756366.2020.1784892
  • Journal Name: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, EMBASE, Food Science & Technology Abstracts, MEDLINE, Directory of Open Access Journals, Index Chemicus (IC)
  • Page Numbers: pp.1422-1432
  • Keywords: Benzylamine, enzyme inhibition, heterocyclic ring, MAO enzymes, molecular docking, MONOAMINE-OXIDASE-B, HYDRAZONE DERIVATIVES, DESIGN, SOLUBILITY, SAFINAMIDE, PREDICTION
  • Anadolu University Affiliated: Yes

Abstract

Many studies have been conducted on the selective inhibition of human monoamine oxidase B (hMAO-B) enzyme using benzylamine-sulphonamide derivatives. Using various chemical modifications onBB-4h, which was reported previously by our team and showed a significant level of MAO-B inhibition, novel benzylamine-sulphonamide derivatives were designed, synthesised, and their MAO inhibition potentials were evaluated. Among the tested derivatives, compounds4iand4tachieved IC(50)values of 0.041 +/- 0.001 mu M and 0.065 +/- 0.002 mu M, respectively. The mechanism ofhMAO-B inhibition by compounds4iand4twas studied using Lineweaver-Burk plot. The nature of inhibition was also determined to be non-competitive. Cytotoxicity tests were conducted and compounds4iand4twere found to be non-toxic. Molecular docking studies were also carried out for compound4i, which was found as the most potent agent, withinhMAO-B catalytic site.