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Identification of Borinic Esters as Inhibitors of Bacterial Cell Growth and Bacterial Methyltransferases, CcrM and MenH

As bacteria continue to develop resistance toward current antibiotics, we find ourselves in a continual battle to identify new antibacterial agents and targets. We report herein a class of boron-containing compounds termed borinic esters that have broad spectrum antibacterial activity with minimum i...

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Published in:Journal of medicinal chemistry 2005-11, Vol.48 (23), p.7468-7476
Main Authors: Benkovic, Stephen J, Baker, Stephen J, Alley, M. R. K, Woo, Youn-Hi, Zhang, Yong-Kang, Akama, Tsutomu, Mao, Weimin, Baboval, Justin, Rajagopalan, P. T. Ravi, Wall, Mark, Kahng, Lyn Sue, Tavassoli, Ali, Shapiro, Lucy
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cited_by cdi_FETCH-LOGICAL-a478t-409ad9bc5134239bf7dfcef6fed51248d3a79c7eb027ee7733e85bbb31c4d2ac3
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container_issue 23
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creator Benkovic, Stephen J
Baker, Stephen J
Alley, M. R. K
Woo, Youn-Hi
Zhang, Yong-Kang
Akama, Tsutomu
Mao, Weimin
Baboval, Justin
Rajagopalan, P. T. Ravi
Wall, Mark
Kahng, Lyn Sue
Tavassoli, Ali
Shapiro, Lucy
description As bacteria continue to develop resistance toward current antibiotics, we find ourselves in a continual battle to identify new antibacterial agents and targets. We report herein a class of boron-containing compounds termed borinic esters that have broad spectrum antibacterial activity with minimum inhibitory concentrations (MIC) in the low microgram/mL range. These compounds were identified by screening for inhibitors against Caulobacter crescentus CcrM, an essential DNA methyltransferase from Gram negative α-proteobacteria. In addition, we demonstrate that borinic esters inhibit menaquinone methyltransferase in Gram positive bacteria using a new biochemical assay for MenH from Bacillus subtilis. Our data demonstrate the potential for further development of borinic esters as antibacterial agents as well as leads to explore more specific inhibitors against two essential bacterial enzymes.
doi_str_mv 10.1021/jm050676a
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subjects Anti-Bacterial Agents - chemical synthesis
Anti-Bacterial Agents - chemistry
Anti-Bacterial Agents - pharmacology
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Bacillus subtilis
Bacillus subtilis - drug effects
Bacillus subtilis - enzymology
Biological and medical sciences
Borinic Acids - chemical synthesis
Borinic Acids - chemistry
Borinic Acids - pharmacology
Caulobacter crescentus
Caulobacter crescentus - drug effects
Caulobacter crescentus - enzymology
DNA Modification Methylases - antagonists & inhibitors
DNA Modification Methylases - chemistry
Esters - chemical synthesis
Esters - chemistry
Esters - pharmacology
Gram-Negative Bacteria - drug effects
Gram-Negative Bacteria - enzymology
Gram-Negative Bacteria - growth & development
Gram-Positive Bacteria - drug effects
Gram-Positive Bacteria - enzymology
Gram-Positive Bacteria - growth & development
Kinetics
Medical sciences
Microbial Sensitivity Tests
Pharmacology. Drug treatments
Proteobacteria - enzymology
Structure-Activity Relationship
title Identification of Borinic Esters as Inhibitors of Bacterial Cell Growth and Bacterial Methyltransferases, CcrM and MenH
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