Aromatic hydrazides: A potential solution for Acinetobacter baumannii infections

Keith D. Green; Nishad Thamban Chandrika; Loan Y. Vu; Allan H. Pang; Oleg V. Tsodikov; Sylvie Garneau-Tsodikova

doi:10.1016/j.ejmech.2023.115165

Aromatic hydrazides: A potential solution for Acinetobacter baumannii infections

Keith D. Green, Nishad Thamban Chandrika, Loan Y. Vu, Allan H. Pang, Oleg V. Tsodikov, Sylvie Garneau-Tsodikova

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

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.

Original language	English
Article number	115165
Journal	European Journal of Medicinal Chemistry
Volume	249
DOIs	https://doi.org/10.1016/j.ejmech.2023.115165
State	Published - Mar 5 2023

Bibliographical note

Publisher Copyright:
© 2023 Elsevier Masson SAS

Funding

Some NMR data reported in this publication were recorded on a Bruker AVANCE NEO 600 MHz high-performance digital NMR spectrometer supported by a NIH S10 grant S10OD28690 (to S.G.-T.). We thank the University of Kentucky PharmNMR Center (in the College of Pharmacy ) for NMR support. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sylvie Garneau-Tsodikova reports a relationship with University of Kentucky that includes a patent “Monohydrazide Compounds with AntiAcinetobacter baumannii Activity” pending to University of Kentucky.Some NMR data reported in this publication were recorded on a Bruker AVANCE NEO 600 MHz high-performance digital NMR spectrometer supported by a NIH S10 grant S10OD28690 (to S.G.-T.). We thank the University of Kentucky PharmNMR Center (in the College of Pharmacy) for NMR support.

Funders	Funder number
National Institutes of Health (NIH)	S10OD28690
University of Kentucky

Keywords

Antibacterial
Bacteriostatic agent
Drug resistance
ESKAPE pathogen
Narrow spectrum

ASJC Scopus subject areas

Pharmacology
Drug Discovery
Organic Chemistry

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10.1016/j.ejmech.2023.115165

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title = "Aromatic hydrazides: A potential solution for Acinetobacter baumannii infections",

abstract = "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.",

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author = "Green, {Keith D.} and {Thamban Chandrika}, Nishad and Vu, {Loan Y.} and Pang, {Allan H.} and Tsodikov, {Oleg V.} and Sylvie Garneau-Tsodikova",

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Aromatic hydrazides: A potential solution for Acinetobacter baumannii infections

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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