Evolution and development of potent monobactam sulfonate candidate IMBZ18g as a dual inhibitor against MDR Gram-negative bacteria producing ESBLs.

A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria. Compound (IMBZ18G) is highly effective and against clinically intractable multi-drug-resistant (MDR) Gram-negative strains, with a highly druglike nature. The checkerboard assay reveals its significant synergistic effect with -lactamase inhibitor avibactam, and the MIC values against MDR were reduced up to 4-512 folds X-ray co-crystal and chemoproteomic assays indicate that the anti-MDR bacteria effect of results from the dual inhibition of the common PBP3 and some class A and C -lactamases. Accordingly, preclinical studies of alone and ‒avibactam combination as potential innovative candidates are actively going on, in the treatment of -lactamase-producing MDR Gram-negative bacterial infections.