Synthesis, biological evaluation and 3D QSAR study of 2,4-disubstituted quinolines as anti-tuberculosis agents

•Three new series of ring-substituted quinolines have been synthesized.•The most promising compounds from the series exhibited MIC99 ranged in 3.125–6.25 μg/mL against M. tuberculosis H37Rv strain.•None of the compounds exhibited cytotoxicity up to the highest test concentration of 200 μg/mL.•The molecular modeling study (3D-QSAR) led to establishing structure activity relationship of compounds.

The synthesis and anti-tuberculosis activity for three series of 2,4-disubstituted quinolines is reported. The synthesized compounds were evaluated for activity against M. tuberculosis H37Rv strain; most promising compounds from the series exhibited MIC99 values ranged between 3.125 and 6.25 μg/mL. None of the compounds exhibited cytotoxicity up to the highest test concentration of 200 μg/mL. To understand the relationship between structure and activity, a 3D-QSAR analysis has been carried out by Comparative Molecular Field Analysis (CoMFA). Atom-fit alignment provided the best model, and allowed prediction of the activity of molecules in the test sets leading to the rationalization of the relationship between structure and activity.

Graphical abstractThree series of ring-substituted quinolines have been synthesized and evaluated for anti-tuberculosis activity. To understand the structure activity relationship, the synthesized analogs were also examined by 3D-QSAR study.Figure optionsDownload full-size imageDownload as PowerPoint slide