Antimicrobial and Antifungal Study of Thiazolotriazolium Salts: In Vivo Investigation, and Molecular Docking

Abstract

Three thiazolo[3,2-b][1,2,4]triazol-7-ium hexabromotellurates 1-3 were synthesized via the electrophilic heterocyclization of methallyl thioether precursors using a classical tellurium(IV) electrophilic reagent generated in situ from TeO2 and 1 M hydrobromic acid. The resulting salts were comprehensively screened for the antimicrobial activity against five clinically relevant pathogens: Staphylococcus aureus, Candida albicans, Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa. Biological assays revealed that compound 1 containing a 2-(4-pyridyl) substituent demonstrated the strongest activity profile, particularly against C. albicans (MIC = 15.625 μg mL-1) and E. coli (MIC = 31.25 μg mL-1). Compound 2, substituted with the 3-hydroxyphenyl moiety, also showed a significant antifungal efficacy, while compound 3 (with the 2-phenyl substituent) exhibited a relatively low activity. To rationalize these differences, the molecular docking was performed targeting MurB (UDP-N-acetylenolpyruvoylglucosamine reductase, PDB 1MBT) and DNA gyrase B (GyrB, PDB 4URO), two bacterial enzymes known to be essential for the viability of Gram-negative pathogens. The docking results confirmed the experimental data, showing strong π–π stacking and hydrogen bonding between compound 1 and the FAD-containing binding pocket of MurB. This work highlights the utility of the tellurium-induced annulation in producing biologically potent heterocycles and emphasizes the structure–activity relationships driven by substituents in position 2 of the fused scaffold.