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

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Cavusoglu B. K., SAĞLIK B. N., OSMANİYE D., LEVENT S., ACAR ÇEVİK U., KARADUMAN A. B., ...More

MOLECULES, vol.23, no.1, 2018 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 23 Issue: 1
  • Publication Date: 2018
  • Doi Number: 10.3390/molecules23010060
  • Journal Name: MOLECULES
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Keywords: thiosemicarbazone, MAO-A, MAO-B, docking, MTT, enzyme kinetic study, ADME, ALZHEIMERS-DISEASE, B INHIBITORS, SOLUBILITY, HYDRAZONE, CHELATORS, DOCKING, SERIES
  • Anadolu University Affiliated: Yes

Abstract

Twenty-six novel thiosemicarbazone derivative B1-B26 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 (H-1- and C-13-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. N-Cyclohexyl-2-[4-[(4-chlorophenyl)thio]benzylidene]hydrazine-1-carbothioamide (B24) was the most active compound against MAO-A. The enzyme kinetics study revealed that compound B24 has a reversible and competitive mode of binding. Interaction modes between compound B24 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 B24 make this compound a promising MAO-A inhibitor.