Aromatic hydrazides: A potential solution for Acinetobacter baumannii infections

The emergence of multidrug-resistant bacteria and the poor efficacy of available antibiotics against these in-fections have led to the urgent need for novel antibiotics. Acinetobacter baumannii is one of high-priority path-ogens 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-mu M inhibitors of A. baumannii growth, with MIC values in the range of 8 mu g/mL to <= 0.125 mu g/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.

Automated summary

The emergence of multidrug-resistant bacteria and the poor efficacy of available antibiotics have led to the urgent need for novel antibiotics. In this study, we synthesized a series of 46 aromatic hydrazides as potential treatments for A. baumannii infections. 34 compounds showed low-to sub-mu M inhibitory effects on A. baumannii growth and demonstrated high potency against multidrug-resistant clinical isolates, while being non-toxic to mammalian cells. These compounds have the potential to be developed into a selective anti-A. baumannii antibiotic.