Synthesis and evaluation of 1, 2, 3-triazole benzoate derivatives for inhibition of serine β-lactamases in extensively drug resistant pathogenic E. coli strains

Abstract

The β-lactamase enzyme is a leading cause of drug resistance developed by bacteria. The combination of β-lactam (BL) antibiotics with an appropriate β-lactamase inhibitor (BLI) is a fundamental approach used to circumvent the problem of β-lactamase mediated resistance. In the present study, non-repeated eight clinical E. coli strains were used in the study. Prior to the screening of synthesized compounds, E. coli strains were phenotypically and genotypically characterized on the basis of MIC and PCR amplification respectively. All newly synthesized thirty-five 1, 2, 3-triazole benzoate derivatives were screened against extended-spectrumtrum β-lactamase class A, class B and class C producing clinical E. coli strains. A zone of inhibition was observed against a class C ESBL trait-bearing isolate with a combination disc containing PB 4 and Cefoxitin indicated the inhibitory activity of PB 4. Similarly, inhibitions by PB 6, PB 7, PB 8, PB 9, PB 15, PB 30 and Cefotaxime against class-A ESBL trait-bearing isolates are indicative of class A ESBL inhibitor capacity of these compounds. In conclusion, cefoxitin in combination with PB 4 and cefotaxime in combination PB 6, PB 7, PB 8, PB 9, PB 15, and PB 30 overcomes the class C and class A β-lactamase enzymatic activity respectively in E. coli strains.

Keywords

• MDR
• β-lactam antibiotics
• β-lactamase
• β-lactamase inhibitors
• 1, 2, 3-triazole benzoate