Synthesis, biological evaluation, and molecular docking studies of novel 3-aryl-5-(alkyl-thio)-1H-1,2,4-triazoles derivatives targeting Mycobacterium tuberculosis

TitleSynthesis, biological evaluation, and molecular docking studies of novel 3-aryl-5-(alkyl-thio)-1H-1,2,4-triazoles derivatives targeting Mycobacterium tuberculosis
Publication TypeJournal Article
Year of Publication2017
AuthorsRode, ND, Sonawane, AD, Nawale, L, Khedkar, VM, Joshi, RA, Likhite, AP, Sarkar, D, Joshi, RR
JournalChemical Biology & Drug Design
Volume90
Issue6
Pagination1206-1214
Date PublishedDEC
Type of ArticleArticle
Abstract

A small library of new 3-aryl-5-(alkyl-thio)-1H-1,2,4-triazoles was synthesized and screened for the antimycobacterial potency against Mycobacterium tuberculosis H37Ra 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)0.03-5.88g/ml for dormant stage and 20 compounds in the range of 0.03-6.96g/ml for active stage. Their lower toxicity (>100g/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 CYP121 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.

DOI10.1111/cbdd.13040
Type of Journal (Indian or Foreign)

Foreign

Impact Factor (IF)

2.802

Divison category: 
Organic Chemistry