Synthesis, Biological Evaluation, and Molecular Docking of Tellurium‐Containing Benzothiazole Derivatives as Enzyme Inhibitors of DNA Gyrase and Dihydrofolate Reductase

Tellurium-containing heterocycles represent an emerging class of organochalcogen compounds with notable redox properties and antimicrobial potential. Incorporation of tellurium into sulfur- and nitrogen-containing frameworks can enhance biological activity through increased polarizability and favorable noncovalent interactions. In this study, a series of novel alkenyl and alkynyl thio-derivatives of 2-mercaptobenzothiazole were synthesized via electrophilic heterocyclization with tellurium tetrahalides and evaluated for antibacterial and antibiofilm activity. The resulting benzothiazolium tellurate derivatives were characterized by IR and 1H/13C NMR spectroscopy, RF values, and elemental analysis. Antibacterial testing against Staphylococcus aureus and Escherichia coli revealed minimum inhibitory concentration (MIC) values ranging from 31.25 to 250 μg/mL and minimum bactericidal concentration (MBC) values of 62.5-500 μg/mL, with alkynyl- and alkenyl-substituted derivatives displaying the highest activity. Several compounds also demonstrated pronounced inhibition of biofilm formation at sub-MIC concentrations. Molecular docking studies were performed against bacterial DNA gyrase B and dihydrofolate reductase (DHFR). The most active alkynyl derivative exhibited favorable binding within the ATP-binding pocket of S. aureus gyrase B, whereas selected alkenyl derivatives showed stable accommodation in the active site of E. coli DHFR. Predicted binding energies ranged from -4.9 to -6.7 kcal/mol, consistent with moderate but meaningful ligand-enzyme interactions. The results indicate that tellurium-containing benzothiazolium derivatives constitute a promising exploratory scaffold for antimicrobial and antibiofilm agents. Their activity appears to arise from a combination of enzyme binding, electrophilic reactivity, and enhanced electronic interactions introduced by tellurium incorporation, supporting further investigation of these systems in preclinical antimicrobial research.