Synthesis,in vitroenzyme activity and molecular docking studies of new benzylamine-sulfonamide derivatives as selective MAO-B inhibitors
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, cilt.35, sa.1, ss.1422-1432, 2020 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 35 Sayı: 1
- Basım Tarihi: 2020
- Doi Numarası: 10.1080/14756366.2020.1784892
- Dergi Adı: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
- Derginin Tarandığı İndeksler: 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)
- Sayfa Sayıları: ss.1422-1432
- Anahtar Kelimeler: Benzylamine, enzyme inhibition, heterocyclic ring, MAO enzymes, molecular docking, MONOAMINE-OXIDASE-B, HYDRAZONE DERIVATIVES, DESIGN, SOLUBILITY, SAFINAMIDE, PREDICTION
- Bilecik Şeyh Edebali Üniversitesi Adresli: Hayır
Özet
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.