Synthesis and antituberculosis activity of new thiazolylhydrazone derivatives

The increasing clinical importance of drug-resistant mycobacterial pathogens has lent additional urgency to microbiological research and new antimycobacterial compound development. For this purpose, new thiazolylhydrazone derivatives were synthesized and evaluated for antituberculosis activity. The reaction of thiosemicarbazide with acetophenone derivatives gave 1-(1-arylethylidene)thiosemicarbazide (1). The N-(1-arylethylidene)-N′-[4-(indan-5-yl)thiazol-2-yl]hydrazone (3) derivatives were synthesized by reacting 1-(1-arylethylidene)thiosemicarbazide with 1-(5-indanyl)-2-bromoethanone (2). The chemical structure of the compounds was elucidated by elemental analyses, IR, 1H NMR, MS-FAB+ spectral data. Antituberculosis activities of the synthesized compounds were determined by broth microdilution assay, the Microplate Alamar Blue Assay, in BACTEC12B medium and the results were screened in vitro, using BACTEC 460 Radiometric System against Mycobacterium tuberculosis H37Rv (ATCC 27294) at 6.25 μg/ml and some of the tested compounds showed important inhibition ranging from 92% to 96%. The compounds were also investigated for their cytotoxic properties on normal mouse fibroblast (NIH/3T3) cell line and the results obtained here showed that all the compounds used have no significant cytotoxicity at the concentrations under 50 μg/ml.

Thiazolylhydrazone derivatives were investigated for antituberculosis activity against Mycobacterium tuberculosis. The role of the different substitution on phenyl ring on activity was explored in structure–activity relationship investigations.Figure optionsDownload as PowerPoint slide