Chalcone-Benzotriazole Conjugates as New Potential Antimicrobial Agents: Design, Synthesis, Biological Evaluation and Synergism with Clinical Drugs

A series of chalcone-benzotriazole conjugates as new potential antimicrobial agents were synthesized and characterized by H-1 NMR, C-13 NMR, IR and HRMS spectra. Antimicrobial assay manifested that some target compounds gave moderate to good antibacterial and antifungal activities. The N-1 derived benzotriazole 5e and N-2 derived benzotriazole 6a exhibited valuable inhibitory efficacy against some tested strains. Especially, derivative 6a gave superior antifungal efficacies against C. utilis, S. cerevisiae and A. flavus (MIC=0.01, 0.02, 0.02 mu mol/mL, respectively) to Fluconazole. The drug combination of compound 5e or 6a with antibacterial Chloromycin, Norfloxacin and antifungal Fluconazole respectively showed stronger antimicrobial efficiency with less dosage and broader antimicrobial spectrum than their separated use alone. The preliminary interaction with calf thymus DNA revealed that compound 6a could intercalate into DNA to form 6a-DNA supramolecular complex which might be a factor to exert its powerful bioactivity. Molecular docking study indicated strong binding of compound 6a with DNA gyrase. The structural parameters such as molecular orbital energy and molecular electrostatic potential of compound 6a were also investigated, which provided better understanding for its good antimicrobial activity.