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Synthesis, biological evaluation, and molecular docking studies of novel 3‐aryl‐5‐(alkyl‐thio)‐1 H ‐1,2,4‐triazoles derivatives targeting Mycobacterium tuberculosis
Author(s) -
Rode Navnath D.,
Sonawane Amol D.,
Nawale Laxman,
Khedkar Vijay M.,
Joshi Ramesh A.,
Likhite Anjali P.,
Sarkar Dhiman,
Joshi Rohini R.
Publication year - 2017
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13040
Subject(s) - antimycobacterial , mycobacterium tuberculosis , thio , chemistry , in vivo , docking (animal) , cytotoxicity , aryl , stereochemistry , potency , triazole , biological activity , combinatorial chemistry , in vitro , alkyl , tuberculosis , biochemistry , biology , organic chemistry , medicine , microbiology and biotechnology , nursing , pathology
A small library of new 3‐aryl‐5‐(alkyl‐thio)‐1 H ‐1,2,4‐triazoles was synthesized and screened for the antimycobacterial potency against Mycobacterium tuberculosis H 37 Ra strain and Mycobacterium bovis BCG both in active and dormant stage. Among the synthesized library, 25 compounds exhibited promising anti‐ TB activity in the range of IC 50 0.03–5.88 μg/ml for dormant stage and 20 compounds in the range of 0.03–6.96 μg/ml for active stage. Their lower toxicity (>100 μg/ml) and higher selectivity ( SI = >10) against all cancer cell lines screened make them interesting compounds with potential antimycobacterial effects. Furthermore, to rationalize the observed biological activity data and to establish a structural basis for inhibition of M. tuberculosis , the molecular docking study was carried out against a potential target MTB CYP 121 which revealed a significant correlation between the binding score and biological activity for these compounds. Cytotoxicity and in vivo pharmacokinetic studies suggested that 1,2,4‐triazole analogues have an acceptable safety index, in vivo stability and bio‐availability.