Synthesis and antimycobacterial activities of some new thiazolylhydrazone derivatives

Ozadali K., Tan O., Yogeeswari P., Dharmarajan S., BALKAN A.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol.24, no.7, pp.1695-1697, 2014 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 24 Issue: 7
  • Publication Date: 2014
  • Doi Number: 10.1016/j.bmcl.2014.02.052
  • Journal Name: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1695-1697
  • Keywords: Thiazolylhydrazone, Antimycobacterial activity, Cytotoxicity, Docking, TUBERCULOSIS THYMIDYLATE KINASE, IN-VIVO METABOLISM, MYCOBACTERIUM-TUBERCULOSIS, CRYSTAL-STRUCTURE, ANTITUBERCULOSIS ACTIVITY, COMPUTATIONAL APPROACH, INHIBITORS, COMPLEX, RATS, ANTIFUNGAL
  • Hacettepe University Affiliated: Yes

Abstract

This Letter reports the synthesis and evaluation of some thiazolylhydrazone derivatives for their in vitro antimycobacterial activities against Mycobacterium tuberculosis H37Rv. The cytotoxic activities of all compounds were also evaluated. The compounds exhibited promising antimycobacterial activity with MICs of 1.03-72.46 mu M and weak cytotoxicity (8.9-36.8% at 50 mu g/mL). Among them, 1-(4-(1H-1,2,4-triazol-1-yl) benzylidene)-2-(4-(4-nitrophenyl) thiazol-2-yl) hydrazine 10 was found to be the most active compound (MIC of 1.03 mu M) with a good safety profile (16.4% at 50 mu g/mL). Molecular modeling studies were done to have an idea for the mechanism of the action of the target compounds. According the docking results it can be claimed that these compounds may bind most likely to TMPK than InhA or CYP121. (C) 2014 Elsevier Ltd. All rights reserved.