Synthesis, structural characterization and antibacterial activity evaluation of novel quinolone-1,2,3-triazole-benzimidazole hybrids

Abstract

In this investigation, a series of 2-quinolone-benzimidazole hybrids linked by a 1,2,3-triazole moiety were prepared using copper-catalyzed Huisgen 1,3-dipolar cycloaddition and condensation reaction. The newly synthesized compounds were characterized by 1H NMR, 13C NMR, single crystal XRD and HRMS analysis. The density functional theory (DFT) calculations were performed using B3LYP/6–31+G (d,p) basis level set for the optimization of molecular geometries of compounds 7a, 7c, 7f and 7l The conformational analysis predicted the existence of two main conformations: a closed and an open conformation. In vitro antibacterial activity was assessed against Gram-positive bacterium Staphylococcus aureus (S. aureus) and Gram-negative bacterium Escherichia coli (E. coli). The bioassays revealed that compounds 7a, 7c, 7f and 7l inhibited the growth of E. coli at a concentration of 0.14 µmol/mL, which was nearly 2-fold stronger than the control drug ampicillin (0.26 µmol/mL). Besides, compounds 7f and 7l exhibited the most promising activity against S. aureus with MIC and MBC values of 0.07 µmol/mL for 7f and 0.14 µmol/mL for 7l compared to 0.27 µmol/mL for ampicillin. These results were supported by the chemical reactivity parameters and electrostatic surface potential (MEP) obtained using theoretical calculations. Molecular docking study of the most active compounds using DNA gyrase A and DNA gyrase B proteins of S. aureus also confirmed the experimental findings.