Azaindole Based Potentiator of Antibiotics against Gram-Negative Bacteria
- 26 October 2021
- journal article
- research article
- Published by American Chemical Society (ACS) in ACS Infectious Diseases
- Vol. 7 (11), 3009-3024
- https://doi.org/10.1021/acsinfecdis.1c00171
Abstract
We discovered azaindole-based compounds with weak innate activity that exhibit substantial potentiation of antibacterial activities of different antibiotics, viz., rifampicin, erythromycin, solithromycin, and novobiocin in Gram-negative bacteria. In the presence of the azaindole derivatives, these antibiotics exhibited submicromolar minimum inhibitory concentrations (MICs) against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. The fold improvements in MIC of these antibiotics that were otherwise weak or inactive on their own against these bacteria were also observed against drug-resistant clinical isolates. Our studies indicate that this selective potentiation is probably through destabilization of the outer membrane’s integrity, known to be regulated by the lipopolysaccharides (LPS). Thus, the azaindole based compounds described here open opportunities for those antibiotics that are otherwise ineffective due to LPS mediated entry barriers in Gram-negative bacteria.Keywords
Funding Information
- National Institute of Allergy and Infectious Diseases (R01AI136803)
- American Lebanese Syrian Associated Charities
- St Jude???s Children Research Hospital
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