Aromatic hydrazides: A potential solution for Acinetobacter baumannii infections

• Published in: European journal of medicinal chemistry 2023-03, Vol.249, p.115165-115165, Article 115165
• Main Authors: Green, Keith D., Thamban Chandrika, Nishad, Vu, Loan Y., Pang, Allan H., Tsodikov, Oleg V., Garneau-Tsodikova, Sylvie
• Format: Article
• Language: English
• Subjects: Acinetobacter baumannii; Animals; Anti-Bacterial Agents - pharmacology; Antibacterial; Bacteriostatic agent; Drug resistance; Drug Resistance, Multiple, Bacterial; ESKAPE pathogen; Mammals; Microbial Sensitivity Tests; Narrow spectrum
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2023.115165

The emergence of multidrug-resistant bacteria and the poor efficacy of available antibiotics against these infections have led to the urgent need for novel antibiotics. Acinetobacter baumannii is one of high-priority pathogens due to its ability to mount resistance to different classes of antibiotics. In an effort to provide novel agents in the fight against infections caused by A. baumannii, we synthesized a series of 46 aromatic hydrazides as potential treatments. In this series, 34 compounds were found to be low- to sub-μM inhibitors of A. baumannii growth, with MIC values in the range of 8 μg/mL to ≤0.125 μg/mL against a broad set of multidrug-resistant clinical isolates. These compounds were not highly active against other bacteria. We showed that one of the most potent compounds, 3e, was bacteriostatic and inhibitory to biofilm formation, although it did not disrupt the preformed biofilm. Additionally, we found that these compounds lacked mammalian cytotoxicity. The high antibacterial potency and the lack of mammalian cytotoxicity make these compounds a promising lead series for development of a novel selective anti-A. baumannii antibiotic. Image for Table of Content Use Only. [Display omitted] •Novel hydrazides act as selective anti-Acinetobacter baumannii agents.•The hydrazides are active against multidrug-resistant A. baumannii strains.•A. baumannii does not develop resistance to the hydrazides.•The hydrazides are not toxic to mammalian cells.