Résumé
A series of novel Triclosan–Isatin–Isoniazid triads were synthesized and evaluated for antitubercular activity. These hybrids showed potent efficacy against Mycobacterium tuberculosis with low minimum inhibitory concentrations (MICs) ranging from 0.78 to 1.56 μg/mL, along with high selectivity indices, indicating strong activity with minimal cytotoxicity in human macrophages. Time-kill assays revealed bactericidal effects, with some hybrids achieving sustained bacterial growth suppression comparable to INH at equivalent MICs. At higher doses, a 3-log reduction in bacterial viability was achieved within three days, with one triad showing an additional 1-log reduction by day six. Mechanistic evaluation using INH-resistant katG mutant strains revealed reduction in activity, indicating KatG-dependent bioactivation. Cytotoxicity assays confirmed low toxicity (IC50 > 100 μg/mL), underscoring their potential as safe and effective anti-TB agents.
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•Cu-promoted triclosan-isatin hybrids and triclosan-isatin-isoniazid triads were designed and assayed against mycobacteria.•Triclosan-isatin-isoniazid triads (13b, 13d, 13e, 13f, 13g and 13k) are promising compounds against M. tuberculosis.•They exhibit low MIC values and low toxicity on mammalian cells.•These compounds have potent bactericidal efficacy in vitro.•The compounds exhibited better binding in the active site of InhA as compared to isoniazid.