| Autor: |
Alagöz MA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Inonu University, 44280 Malatya, Turkey., Oh JM; Department of Pharmacy, and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Korea., Zenni YN; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Inonu University, 44280 Malatya, Turkey., Özdemir Z; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Inonu University, 44280 Malatya, Turkey., Abdelgawad MA; Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, Al Jouf 72341, Saudi Arabia., Naguib IA; Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia., Ghoneim MM; Department of Pharmacy Practice, Faculty of Pharmacy, AlMaarefa University, Ad Diriyah 13713, Saudi Arabia., Gambacorta N; Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari 'Aldo Moro', Via E. Orabona, 4, 70125 Bari, Italy., Nicolotti O; Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari 'Aldo Moro', Via E. Orabona, 4, 70125 Bari, Italy., Kim H; Department of Pharmacy, and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Korea., Mathew B; Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi 682 041, India. |
| Abstrakt: |
Sixteen compounds ( TR1-TR16 ) were synthesized and evaluated for their inhibitory activities against monoamine oxidase A and B (MAOs). Most of the derivatives showed potent and highly selective MAO-B inhibition. Compound TR16 was the most potent inhibitor against MAO-B with an IC 50 value of 0.17 μM, followed by TR2 (IC 50 = 0.27 μM). TR2 and TR16 selectivity index (SI) values for MAO-B versus MAO-A were 84.96 and higher than 235.29, respectively. Compared to the basic structures, the para -chloro substituent in TR2 and TR16 increased the inhibitory activity of MAO-B. TR2 and TR16 were reversible MAO-B inhibitors that were competitive, with K i values of 0.230 ± 0.004 and 0.149 ± 0.016 µM, respectively. The PAMPA method indicated that compounds TR2 and TR16 had the tendency to traverse the blood-brain barrier. Docking investigations revealed that lead compounds were beneficial for MAO-B inhibition via association with key as well as selective E84 or Y326 residues, but not for MAO-A inhibition via interaction primarily driven by hydrophobic contacts. In conclusion, TR2 and TR16 are therapeutic prospects for the management of multiple neurodegenerative diseases. |
