Synthesis and bioactivity of novel triazole incorporated benzothiazinone derivatives as antitubercular and antioxidant agent

TitleSynthesis and bioactivity of novel triazole incorporated benzothiazinone derivatives as antitubercular and antioxidant agent
Publication TypeJournal Article
Year of Publication2016
AuthorsShaikh, MH, Subhedar, DD, Arkile, MA, Khedkar, VM, Jadhav, NJ, Sarkar, D, Shingate, BB
JournalBioorganic & Medicinal Chemistry Letters
Volume26
Issue2
Pagination561-569
Date PublishedJAN
ISSN0960-894X
Keywords1, 2, 3-Triazole, ADME prediction, Antioxidant, Antitubercular, Docking study
Abstract

In search of new active molecules against Mycobacterium tuberculosis (MTB) H37Ra and M. bovis BCG, a small focused library of benzothiazinone based 1,2,3-triazoles has been efficiently prepared via click chemistry approach. Several derivatives were found to be promising inhibitors of MTB and M. bovis BCG characterized by lower MIC values (27.34-29.37 mu g/mL). Among all the synthesized compounds, 6c and 6e is the most active compound against MTB and M. bovis BCG. The compounds were further tested for anti-proliferative activity against HeLa, A549 and A431 cell lines using MTT assay and showed no significant cytotoxic activity at the maximum concentration evaluated. Further, the synthesized compounds were found to have potential antioxidant activity with IC50 range = 14.14-47.11 mu g/mL. Furthermore, to rationalize the observed biological activity data, the molecular docking study also been carried out against a potential target MTB DprE1, which revealed a significant correlation between the binding score and biological activity for these compounds. The results of the in vitro and in silico study suggest that the triazole incorporated benzothiazinone may possess the ideal structural requirements for further development of novel therapeutic agents. (C) 2015 Elsevier Ltd. All rights reserved.

DOI10.1016/j.bmcl.2015.11.071
Type of Journal (Indian or Foreign)

Foreign

Impact Factor (IF)

2.486

Divison category: 
Biochemical Sciences