Furan–thiazole hydrazone scaffolds as promising antitubercular and antibacterial agents: synthesis, characterization, bioevaluation and computational analysis

In the search for novel therapeutic agents against tuberculosis and bacterial infections, a series of furan–thiazole hydrazone derivatives (4a–4n) was synthesized, characterized and evaluated for antitubercular and antibacterial properties. The furan–thiazole hydrazone derivatives were characterized using FT-IR, ¹H NMR, ¹³C{¹H} NMR, ¹⁹F NMR and HRMS methods. The synthesized compounds were tested in vitro against Mycobacterium tuberculosis H37Rv, Staphylococcus aureus, and Escherichia coli. Compounds 4a, 4b and 4c exhibited good antitubercular activity with MIC values of 3.12 μg mL⁻¹, comparable to the standard drug pyrazinamide. In antibacterial assays, compound 4g, bearing a trifluoromethoxy group, demonstrated superior efficacy with inhibition zones of 19 mm (S. aureus) and 17 mm (E. coli). Molecular docking studies further validated these findings, revealing strong binding affinities of compounds 4a–4c with M. tuberculosis CYP51 (−10.32 to −10.76 kcal mol⁻¹) and compound 4g with 2,2-dialkylglycine decarboxylase (−9.65 kcal mol⁻¹), suggesting effective interaction with key active site residues. In silico ADME profiling revealed favorable drug-likeness and pharmacokinetics for most compounds, while DFT studies including structure optimization, FMO analysis, reactivity descriptors, and MEP mapping offered valuable insights into electronic distribution, reactivity, and potential binding sites of the furan–thiazole hydrazone derivatives. The results support the candidacy of compounds 4a, 4b and 4c in antitubercular study, while 4f and 4g as notable antibacterial agents for future development.