Anti-tubercular agents. Part 7: A new class of diarylpyrrole–oxazolidinone conjugates as antimycobacterial agents

• Published in: European journal of medicinal chemistry 2013-06, Vol.64, p.239-251
• Main Authors: Kamal, Ahmed, Swapna, P., Shetti, Rajesh V.C.R.N.C., Shaik, Anver Basha, Narasimha Rao, M.P., Sultana, Farheen, Khan, Inshad Ali, Sharma, Sandeep, Kalia, Nitin Pal, Kumar, Sunil, Chandrakant, Bagul
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Anti-tubercular agents; Antibacterial; Cell Line; Dose-Response Relationship, Drug; Gram-Positive Bacteria - drug effects; MDR- and XDR-TB; Mice; Microbial Sensitivity Tests; Models, Molecular; Molecular Structure; Mycobacterium tuberculosis; Oxazolidinones; Oxazolidinones - chemistry; Oxazolidinones - pharmacology; Pyrroles - chemistry; Pyrroles - pharmacology; Structure-Activity Relationship
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2013.03.027

In an effort to discover new anti-tubercular agents, a series of new diarylpyrrole–oxazolidinone conjugates have been designed and synthesized. The anti-tubercular activity of these new conjugates (4a–n and 5a–d) against Mycobacterium tuberculosis H37Rv and drug resistance strains such as M. tuberculosis RifR and M. tuberculosis XDR are discussed, wherein compound 4i has been found to be the most potent amongst the series. MTT assay was performed on the active conjugates of the series (4b–f, 4i and 5c) against mouse macrophage (J-774) cells to evaluate cytotoxic effects and selective index values. In addition, these conjugates (4a–n and 5a–d) are also tested against a panel of Gram-positive and Gram-negative bacterial strains. The docking studies have been carried out to provide some insight into the mechanism of action for this class of compounds. [Display omitted] A series of new diarylpyrrole–oxazolidinone conjugates have been synthesized and evaluated for their in vitro anti-tubercular activity. Further these compounds were also evaluated for their antibacterial activity. •A new class of diarylpyrrole–oxazolidinone conjugates designed and synthesized.•The compounds (4a–n and 5a–d) evaluated for their anti-tubercular activity.•Compound 4i exhibited prominent inhibitory activity (MIC 2.0 μg/mL).•These compounds also tested for their antibacterial activity.•Performed docking studies provided some insight into the mechanism of action.