Azaindole Based Potentiator of Antibiotics against Gram-Negative Bacteria

• DOI: 10.1021/acsinfecdis.1c00171
• Publication Date: 2021-10-26T17:15:02Z
• Authors: Sreevalli Sharma; Ranga Rao; Stephanie M. Reeve; Gregory A. Phelps; Nagakumar Bharatham; Nainesh Katagihal...; Vasanthi Ramachan...; Savitha Raveendran; Maitrayee Sarma; Anubha Nath; Teby Thomas; Dhanasekaran Mani...; Savitha Nagaraj; V. Balasubramanian; Richard E. Lee; Shahul Hameed P; Santanu Datta
• Keywords: Novobiocin; Acinetobacter baumannii; Gram-Negative Bacteria

We discovered azaindole-based compounds with weak innate activity that exhibit substantial potentiation of antibacterial activities different antibiotics, viz., rifampicin, erythromycin, solithromycin, and novobiocin in Gram-negative bacteria. In the presence azaindole derivatives, these antibiotics exhibited submicromolar minimum inhibitory concentrations (MICs) against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii. The fold improvements MIC were otherwise or inactive on their own bacteria also observed drug-resistant clinical isolates. Our studies indicate this selective is probably through destabilization outer membrane's integrity, known to be regulated by lipopolysaccharides (LPS). Thus, based described here open opportunities for those are ineffective due LPS mediated entry barriers