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Design and synthesis of 4-[4-formyl-3-(2-naphthyl)pyrazol-1-yl]benzoic acid derivatives as potent growth inhibitors of drug-resistant Staphylococcus aureus

The Journal of Antibiotics volume 73, pages 818–827 (2020)Cite this article

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Abstract

We report the synthesis and antimicrobial studies of a new series of naphthyl-substituted pyrazole-derived hydrazones. Many of these novel compounds are potent growth inhibitors of several strains of drug-resistant bacteria. These potent compounds have inclined growth inhibitory properties for planktonic Staphylococcus aureus and Acinetobacter baumannii, and its drug-resistant variants with minimum inhibitory concentration (MIC) as low as 0.78 and 1.56 µg ml−1, respectively. These compounds also show potent activity against S. aureus and A. baumannii biofilm formation and eradication properties. Time Kill Assay shows that these compounds are bactericidal for S. aureus and bacteriostatic for A. baumannii. The probable mode of action is the disruption of the bacterial cell membrane. Furthermore, potent compounds are nontoxic to human cell lines at several fold higher concentrations than the MICs.

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Acknowledgements

This publication was made possible by the Research Technology Core of the Arkansas INBRE program, supported by a grant from the National Institute of General Medical Sciences, (NIGMS), P20 GM103429 from the National Institutes of Health to record the Mass Spectrometry data. This publication was made possible by the Arkansas INBRE program, supported by a grant from the National Institute of General Medical Sciences, (NIGMS), P20 GM103429 from the National Institutes of Health, grant number P20 GM109005 (AGB). ABI mini-grant 200027 also helped to accomplish this manuscript.

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Authors and Affiliations

  1. Department of Chemistry and Physics, College of Science and Mathematics, Arkansas State University, Jonesboro, AR, 72467, USA

    Rawan Alnufaie, Nickolas Alsup, Hansa Raj KC, Matthew Newman, Jedidiah Whitt, Steven Andrew Chambers & Mohammad A. Alam

  2. Department of Biological Sciences, College of Science and Mathematics, Arkansas State University, Jonesboro, AR, 72467, USA

    David Gilmore

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41429_2020_341_MOESM1_ESM.docx

Design, and Synthesis of 4-[4-Formyl-3-(2-naphthyl)pyrazol-1-yl]benzoic acid Derivatives as Potent Growth Inhibitors of Drug-Resistant Staphylococcus aureus

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Alnufaie, R., Alsup, N., KC, H.R. et al. Design and synthesis of 4-[4-formyl-3-(2-naphthyl)pyrazol-1-yl]benzoic acid derivatives as potent growth inhibitors of drug-resistant Staphylococcus aureus. J Antibiot 73, 818–827 (2020). https://doi.org/10.1038/s41429-020-0341-2

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