Chemical synthesis and biological evaluation of triazole derivatives as inhibitors of InhA and antituberculosis agents

A series of triazoles have been prepared and evaluated as inhibitors of InhA as well as inhibitors of Mycobacterium tuberculosis H37Rv. Several of these new compounds possess a good activity against InhA, particularly compounds 17 and 18 for which molecular docking has been performed. Concerning their activities against M. tuberculosis H37RV strain, two of them, 3 and 12, were found to be good inhibitors with MIC values of 0.50 and 0.25 μg/mL, respectively. Particularly, compound 12 presenting the best MIC value of all compounds tested (0.6 μM) is totally inactive against InhA.

Graphical abstractA series of 1,4-disubstituted triazole derivatives were synthetized and evaluated against InhA and Mycobacterium tuberculosis H37Rv. Two compounds show antimycobacterial activities with MIC values in the low micromolar range.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Synthesis of 1,2,3-triazoles. ► Evaluation of triazole derivatives as inhibitors of InhA. ► One compound displayed inhibitory activity of 0.6 μM against M. tuberculosis H37Rv.