Synthesis and antimycobacterial activities of some new thiazolylhydrazone derivatives

• Published in: Bioorganic & medicinal chemistry letters 2014-04, Vol.24 (7), p.1695-1697
• Main Authors: Ozadali, Keriman, Unsal Tan, Oya, Yogeeswari, Perumal, Dharmarajan, Sriram, Balkan, Ayla
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antimycobacterial activity; Cell Line, Tumor; Cell Proliferation - drug effects; Cytotoxicity; Docking; Dose-Response Relationship, Drug; Humans; Hydrazones - chemical synthesis; Hydrazones - chemistry; Hydrazones - pharmacology; Microbial Sensitivity Tests; Molecular Docking Simulation; Molecular Structure; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Structure-Activity Relationship; Thiazoles - chemical synthesis; Thiazoles - chemistry; Thiazoles - pharmacology; Thiazolylhydrazone
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2014.02.052

The novel thiazolylhydrazones displayed encouraging antimycobacterial activity with low cytotoxicity. Docking studies were performed with selected enzymes, CYP121, InhA and TMPK of M. tuberculosis. 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 1.03–72.46μM and weak cytotoxicity (8.9–36.8% at 50μg/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 1.03μM) with a good safety profile (16.4% at 50μg/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.