Identification of borinic esters as inhibitors of bacterial cell growth and bacterial methyltransferases, CcrM and MenH

Stephen J. Benkovic, Stephen J. Baker, M. R.K. Alley, Youn Hi Woo, Yong Kang Zhang, Tsutomu Akama, Weimin Mao, Justin Baboval, P. T.Ravi Rajagopalan, Mark Wall, Lyn Sue Kahng, Ali Tavassoli, Lucy Shapiro

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)7468-7476
Number of pages9
JournalJournal of Medicinal Chemistry
Volume48
Issue number23
DOIs
StatePublished - Nov 17 2005

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

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    Benkovic, S. J., Baker, S. J., Alley, M. R. K., Woo, Y. H., Zhang, Y. K., Akama, T., Mao, W., Baboval, J., Rajagopalan, P. T. R., Wall, M., Kahng, L. S., Tavassoli, A., & Shapiro, L. (2005). Identification of borinic esters as inhibitors of bacterial cell growth and bacterial methyltransferases, CcrM and MenH. Journal of Medicinal Chemistry, 48(23), 7468-7476. https://doi.org/10.1021/jm050676a