Design, synthesis and 3D-QSAR studies of new diphenylamine containing 1,2,4-triazoles as potential antitubercular agents

• A series of triazole derivatives having diphenyl amine moiety were synthesized.
• Synthesized compounds were evaluated for their ability to inhibit Mtb H37Rv.
• The target compounds 4a, 4d and 4e showed potent antitubercular activity.
• Highly predictive CoMFA and CoMSIA models were developed.

A new series of new diphenylamine containing 1,2,4-triazoles were synthesized from 4-arylideneamino-5-[2-(2,6-dichlorophenylamino) benzyl]-2H-1,2,4-triazole-3(4H)-thiones 3a–f. The synthesized compounds were screened for in-vitro antimycobacterial and antibacterial activities. The synthesized compounds 4a, 4e and 4d have shown potential activity against Mycobacterium tuberculosis H37Rv strain with MIC of 0.2, 1.6 and 3.125 μM respectively. To investigate the SAR of diphenylamine containing 1,2,4-triazole derivatives in more details, CoMFA (q2-0.432, r2-0.902) and CoMSIA (q2-0.511, r2-0.953) models on M. tuberculosis H37Rv were established. The generated 3D-QSAR models are externally validated and have shown significant statistical results, and these models can be used for further rational design of novel diphenylamine containing 1,2,4-triazoles as potent antitubercular agents.

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