Synthesis and MAO inhibitory activity of novel thiazole-hydrazones

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ATLI EKLİOĞLU Ö., ÖZKAY Y.

TURKISH JOURNAL OF CHEMISTRY, vol.41, no.5, pp.685-699, 2017 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 41 Issue: 5
  • Publication Date: 2017
  • Doi Number: 10.3906/kim-1612-78
  • Journal Name: TURKISH JOURNAL OF CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, TR DİZİN (ULAKBİM)
  • Page Numbers: pp.685-699
  • Keywords: Thiazole, hydrazone, hMAO enzymes, enzyme inhibition, MONOAMINE-OXIDASE INHIBITORS, BIOLOGICAL EVALUATION, DERIVATIVES, DESIGN, PERMEABILITY, PREDICTION, DISORDERS, ANALOGS, MOIETY, ENZYME
  • Anadolu University Affiliated: Yes

Abstract

A series of new thiazole-hydrazones (3a-3n) were synthesized, characterized, and screened for their hMAO-A and hMAO-B inhibitory activity by an in vitro fluorometric method. Selectivity indexes (SIs) were expressed as IC50 (MAO-A) / IC50 (MAO-B). Compound 3f showed promising hMAO-A inhibition with an IC50 value of 1.20 mu M and displayed a very significant SI of 0.04 towards hMAO-A. The mechanism of hMAO-A inhibition was investigated by enzyme kinetics using Lineweaver-Burk graphics. Compound 3f was further screened for its cytotoxicity by using a healthy NIH/3T3 mouse embryonic fibroblast cell line (ATCC CRL1658) and was evaluated as nontoxic at its effective concentration against hMAO-A. The ADME prediction of the compounds revealed that they may have good pharmacokinetic profiles, which is necessary for drug candidates.