Synthesis of 4,4'-(4-Formyl-1 H-pyrazole-1,3-diyl)dibenzoic Acid Derivatives as Narrow Spectrum Antibiotics for the Potential Treatment of Acinetobacter Baumannii Infections

Evan Delancey; Devin Allison; Hansa Raj Kc; David F Gilmore; Todd Fite; Alexei G Basnakian; Mohammad A Alam

doi:10.3390/antibiotics9100650

Synthesis of 4,4'-(4-Formyl-1 H-pyrazole-1,3-diyl)dibenzoic Acid Derivatives as Narrow Spectrum Antibiotics for the Potential Treatment of Acinetobacter Baumannii Infections

Antibiotics (Basel). 2020 Sep 28;9(10):650. doi: 10.3390/antibiotics9100650.

Authors

Evan Delancey¹, Devin Allison¹, Hansa Raj Kc¹, David F Gilmore², Todd Fite^{3

4}, Alexei G Basnakian^{3

4}, Mohammad A Alam¹

Affiliations

¹ Department of Chemistry and Physics, College of Science and Mathematics, Arkansas State University, Jonesboro, AR 72467, USA.
² Department of Biological Sciences, College of Science and Mathematics, Arkansas State University, Jonesboro, AR 72467, USA.
³ Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock, AR 72205, USA.
⁴ Central Arkansas Veterans Healthcare System, W. 7th St., Little Rock, AR 72205, USA.

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.

Keywords: Acinetobacter baumannii; antimicrobial; hydrazone; narrow-spectrum antibiotics; pyrazole; toxicity.

Abstract

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