Molecular hybrid of 1,2,3-triazole and schiff base as potential antibacterial agents: DFT, molecular docking and ADME studies

•Hybrid compounds of 1,2,3-triazole and Schiff bases were successfully synthesized.•Most of the compounds showed significant activity against the bacterial strains.•Compounds 7, 9, 10, 11, 12 and 15 exhibited higher activity amongst the tested compounds.•Most of the compounds exhibit desirable physicochemical properties for druglikeness. Hybrid drugs help combat antibacterial drug resistance, which is an increasing problem globally. In addition to saving time and money, hybrid drugs offer multiple benefits. Using the triazole precursor compound 5 in conjunction with primary amines, a series of novel 1,2,3-triazole and Schiff base compounds were synthesized (6–16). Their chemical structures were characterized using 1H NMR, 13C NMR, FTIR, CHN-elemental, high-resolution mass spectrometry and SC-XRD analyses. All the compounds showed good antibacterial activities against twelve bacterial strains at different concentrations. From the minimum inhibitory concentration and cytotoxicity studies, compounds 7, 9, 10, 11, 12 and 15 were selected as the most potent potential drug candidates against Mycobacterium smegmatis, Proteus mirabilis, Escherichia coli and Klebsiella pneumonia. Molecular docking studies of the most active compounds were done against their specific bacteria targets. Experimentally observed structure-activity relationships (SARs) for the most active compounds are consistent with molecular docking studies, indicating that benzylic (7 and 9), heterocyclic (10, 11, and 12) and electron-withdrawing (15) subunits enhance antibacterial activity. The absorption, distribution, metabolism, and excretion (ADME) parameter, Molinspiration bioactivity score, and the PreADMET properties revealed that most of the synthesized compounds possess desirable physicochemical properties for druglikeness and may be considered as orally active potential drugs. [Display omitted]