3-Aryl-substituted imidazo[1,2-a]pyridines as antituberculosis agents

Novel inhibitors are needed to tackle tuberculosis. Herein, we report the 3-aryl-substituted imidazo[1,2-a]pyridines as potent antituberculosis agents. A small library of 3-aryl-substituted imidazo[1,2-a]pyridines was synthesized using direct arylation, followed by nitro reduction and finally Pd-catalyzed C-N coupling reactions. The compounds thus obtained were evaluated against Mycobacterium tuberculosis H37Rv. Compound 26 was identified as an antituberculosis lead with a minimum inhibitory concentration of 2.3 mu g/ml against M. tuberculosis H37Rv. This compound showed a selectivity index of 35. The docking of 26 in the active site of the M. tuberculosis cytochrome bc1 complex cytochrome b subunit (Mtb QcrB) revealed key pi-pi interactions of compound 26 with the Tyr389 and Trp312 residues of Mtb QcrB.

Automated summary

A series of 3-aryl-substituted imidazo[1,2-a]pyridines were synthesized through direct arylation, with compound 26 identified as a potent antituberculosis lead against Mycobacterium tuberculosis H37Rv. Compound 26 showed significant π-π interactions with the Tyr389 and Trp312 residues of Mtb QcrB in the active site of the M. tuberculosis cytochrome bc1 complex.