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2‑Aminoimidazole-benzimidazole Conjugates Potentiate the Gram-Positive Selective Antibiotic Clarithromycin against
Ashley N Crotteau1, Ansley M Nemeth1, Roberta J Melander1
1Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States.
Abstract:
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.
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