Synthesis of New Hydrazone Derivatives for MAO Enzymes Inhibitory Activity

• Published in: Molecules (Basel, Switzerland) Switzerland), 2017-08, Vol.22 (8), p.1381
• Main Authors: Can, Nafiz Öncü, Osmaniye, Derya, Levent, Serkan, Sağlık, Begüm Nurpelin, İnci, Beril, Ilgın, Sinem, Özkay, Yusuf, Kaplancıklı, Zafer Asım
• Format: Article
• Language: English
• Subjects: Amine oxidase (flavin-containing); Animals; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - metabolism; Cytotoxicity; Enzyme Activation - drug effects; Enzyme kinetics; Enzymes; Genotoxicity; Humans; hydrazone, MAO enzymes inhibition, docking studies, genotoxicity, cytotoxicity; Hydrazones; Hydrazones - chemical synthesis; Hydrazones - pharmacology; Inhibitory Concentration 50; Kinetics; Mice; Models, Molecular; Molecular Conformation; Molecular Docking Simulation; Molecular Structure; Monoamine Oxidase - metabolism; Monoamine Oxidase Inhibitors - chemical synthesis; Monoamine Oxidase Inhibitors - pharmacology; NIH 3T3 Cells; NMR; Nuclear magnetic resonance; Permeability; Strong interactions (field theory); Structure-Activity Relationship; Studies
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules22081381

In the present work, 14 new 1-substituted-2-phenylhydrazone derivatives were synthesized to evaluate their inhibitory activity against hMAO enzymes. The structures of the newly synthesized hydrazones 2a-2n were characterized by IR, 1H-NMR, 13C-NMR, HR-MS spectroscopic methods. The inhibitory activity of compounds 2a-2n against hMAO-A and hMAO-B enzymes was elucidated by using an in-vitro Amplex Red® reagent assay based on fluorometric methods. According to the activity studies, 2a and 2b were found to be the most active compounds against hMAO-A enzyme, with IC50 values of 0.342 µM and 0.028 µM, respectively. The most active compounds 2a-2b were evaluated by means of enzyme kinetics and docking studies. Moreover, these compounds were subjected to cytotoxicity and genotoxicity tests to establish their preliminary toxicological profiles and were found to be non-cytotoxic and non-genotoxic. Consequently, the findings of this study display the biological importance of compounds 2a, 2b as selective, irreversible and competitive inhibitors of hMAO-A. Docking studies revealed that there is a strong interaction between hMAO-A and the most active compound 2b.