Synthesis and Biological Evaluation of New Thiosemicarbazone Derivative Schiff Bases as Monoamine Oxidase Inhibitory Agents

• Published in: Molecules (Basel, Switzerland) Switzerland), 2017-12, Vol.23 (1), p.60
• Main Authors: Çavuşoğlu, Betül Kaya, Sağlık, Begüm Nurpelin, Osmaniye, Derya, Levent, Serkan, Acar Çevik, Ulviye, Karaduman, Abdullah Burak, Özkay, Yusuf, Kaplancıklı, Zafer Asım
• Format: Article
• Language: English
• Subjects: 3T3 Cells; ADME; Aldehydes; Amine oxidase (flavin-containing); Animals; Binding Sites; Blood-Brain Barrier - metabolism; Cell Survival; Chemical compounds; Chemical reactions; docking; enzyme kinetic study; Enzyme kinetics; Excretion; Hydrazine; Imines; Inhibitors; Kinetics; MAO-A; MAO-B; Metabolism; Mice; Molecular Docking Simulation; Molecular Structure; Monoamine Oxidase - metabolism; Monoamine Oxidase Inhibitors - chemical synthesis; Monoamine Oxidase Inhibitors - chemistry; Monoamine Oxidase Inhibitors - pharmacology; MTT; NMR; Nuclear magnetic resonance; Nuclear reactions; Protein Binding; Reaction kinetics; Schiff Bases - chemical synthesis; Schiff Bases - pharmacology; Structure-Activity Relationship; Thiosemicarbazides; thiosemicarbazone; Thiosemicarbazones - chemical synthesis; Thiosemicarbazones - chemistry; Thiosemicarbazones - pharmacology
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules23010060

Twenty-six novel thiosemicarbazone derivative - were synthesized via condensation reactions between the corresponding thiosemicarbazides and aldehydes. The chemical characterization of the compounds was carried out by infrared (IR), mass (MS), proton and carbon nuclear magnetic resonance (¹H- and C-NMR) spectroscopic analyses. The compounds were investigated for their monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) inhibitory activity and most of them were more potent against MAO-A enzyme when compared with MAO-B enzyme. -Cyclohexyl-2-[4-[(4-chlorophenyl)thio]benzylidene]hydrazine-1-carbothioamide ( ) was the most active compound against MAO-A. The enzyme kinetics study revealed that compound has a reversible and competitive mode of binding. Interaction modes between compound and MAO-A were clarified by docking studies. In addition, the favourable absorption, distribution, metabolism, and excretion (ADME) properties and non-toxic nature of compound make this compound a promising MAO-A inhibitor.