2‑Aminoimidazole-benzimidazole Conjugates Potentiate the Gram-Positive Selective Antibiotic Clarithromycin against Acinetobacter baumannii.

An increase in antibiotic resistance and the paucity of new treatment options have led to the present-day antibiotic resistance crisis. Acinetobacter baumannii is categorized by the World Health Organization as a critical priority. Previously, we reported halogenated aryl 2-aminoimidazole (2-AI) adjuvants that potentiate macrolide antibiotics against A. baumannii; however, this class of adjuvants exhibits cytotoxicity toward HepG2 cells. In this study we generate a library of 2-AI-benzimidazole adjuvants that potentiate clarithromycin (CLR), and exhibit reduced cytotoxicity. Lead compounds lower the CLR minimum inhibitory concentration (MIC) across a panel of A. baumannii clinical isolates, and have therapeutic indices (TI) up to 6-fold higher than the parent 2-AIs.