Abstract
Acinetobacter baumannii has emerged as one of the most lethal drug-resistant bacteria in recent years. We report the synthesis and antimicrobial studies of 25 new pyrazole-derived hydrazones. Some of these molecules are potent and specific inhibitors of A. baumannii strains with a minimum inhibitory concentration (MIC) value as low as 0.78 µg/mL. These compounds are non-toxic to mammalian cell lines in in vitro studies. Furthermore, one of the potent molecules has been studied for possible in vivo toxicity in the mouse model and found to be non-toxic based on the effect on 14 physiological blood markers of organ injury.
Highlights
The ESKAPE pathogens, a group of six bacteria (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) cause the majority of nosocomial infections in the U.S, and these pathogens are effectively escaping the current arsenal of antibiotics [1]
If the causative the infection is known,and thethe use of narrow-spectrum antibiotics can alleviate some of agent theseofproblems
In our efforts to find potent antimicrobial agents [13], we have previously reported the synthesis of phenyl substituted pyrazole derivatives as potent S. aureus and A. baumannii growth inhibitors
Summary
The ESKAPE pathogens, a group of six bacteria (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) cause the majority of nosocomial infections in the U.S, and these pathogens are effectively escaping the current arsenal of antibiotics [1]. 2017, the WHO released a list of 12 drug-resistant bacteria that pose the greatest threat to human health and for which new antibiotics are desperately needed. The discovery of new of 14 antibacterial agents to treat A. baumannii infections is imperative. If the causative agent of the infection is species detrimental effect upon the host microbiome. If the causative the infection is known,and thethe use of narrow-spectrum antibiotics can alleviate some of agent theseofproblems. The discovery of new less collateral damage infections upon the host is an attractive approach fight multidrug-resistance [12].microbiome. It is expected that new drugs to will be multidrug-resistance non-toxic in vivo at antibacterial agents to treat baumannii infections is imperative. Broad-spectrum antibiotics play a vital role in treating bacterial infections, there are
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