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An efficient, green strategy for synthesis of 1,4-disubstituted-1,2,3-triazole has been developed using 1,8-diazabicyclo[5.4.0]­undec-7-ene (DBU) acetate ionic liquid (200 μL) under a solvent- and external base-free condition. This protocol is further applied for the synthesis of novel amino acid containing 1,2,3-triazole molecules, which were then evaluated for potential antitubercular and antibacterial activities. Cytotoxicity assay of the compounds was also performed. In silico analysis of the promising compounds selected through experimental analysis was thereafter performed for visualizing molecular interactions and predicting binding affinities between our synthesized molecules, which exhibited good activity in experimental studies and the DprE1 target protein of Mycobacterium tuberculosis. Durg-likeness studies also show potential of the synthesized molecules as drug candidates.

A straightforward and convenient methodology has been developed for the reaction of 2-aminobenzamide and carbonyls affording 2,3-dihydroquinazolin-4(1H)-ones using aqueous solution of [C 12 Py][FeCl 3 Br]. The developed methodology was applied for the synthesis of 25 quinazolinone-triazole hybrids followed by evaluation of their in vitro anti-tubercular (TB) activity. The results revealed that 8 quinazolinone-triazole hybrids displayed promising activity having MIC values of 0.78−12.5 μg/ mL. The compound 3if with MIC 0.78 μg/mL was found to be the lead nominee among the series, better than Ethambutol, a first line anti-TB drug and comparable with Rifampicin. The active compounds with MIC values ≤ 6.25 μg/mL were subjected to in vitro cytotoxicity and found nontoxic. In drug−drug interaction, compounds 3ia and 3ii interacted synergistically with all the three anti-TB drugs, INH, RFM, and EMB. Other 3 compounds interacted either in synergistic or additive manners. Important information on the binding interaction of the target compounds with the active sites of 1DQY Antigen 85C from Mycobacterium tuberculosis and Enoyl acyl carrier protein reductase (InhA) enzymes was obtained from molecular docking studies. Screening of the drug-likeness properties and bioactivity score indicates that synthesized molecules could be projected as potential drug candidates. Based on the current study, quinazolinone-triazole hybrids framework can be useful in drug development for TB.

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