Design, Synthesis, In Vitro, and In Silico ADME/Toxicity Study of Novel Methoxyphenyl-Substituted Thiazole–Triazole Hybrids as Antitubercular Agents

Objective: A novel series of methoxyphenyl-substituted thiazole–triazole hybrid Schiff base derivatives (PB-06–PB-20) was designed, synthesized, and characterized to evaluate their potential as antitubercular agents. Methods: The compounds were obtained via a multi-step synthetic route involving Hantzsch condensation, hydrazide formation, and Schiff base condensation with various aromatic aldehydes. Their structures were confirmed by FT-IR, 1H, 13C NMR, and mass spectrometry. The antitubercular activity was evaluated against Mycobacterium tuberculosis H37Rv strain using the Alamar Blue assay. Molecular docking studies supported these findings, revealing strong binding affinities of the active derivatives with the M. tuberculosis DprE1 protein. Furthermore, in silico ADME and toxicity profiling indicated favorable drug-like properties and low predicted toxicity. Results and Discussion: Compounds PB-14, PB-18, and PB-20 exhibited promising activity with MIC values of 6.25 µg/mL. Molecular docking studies supported these findings, revealing strong binding affinities of the active derivatives with the M. tuberculosis DprE1 protein. Furthermore, in silico ADME and toxicity profiling indicated favorable drug-like properties and low predicted toxicity, confirming their potential for further development. Conclusions: These results establish thiazole–triazole Schiff bases as promising leads for novel antitubercular drug discovery.