Synthesis and evaluation of quinazolines as inhibitors of the bacterial cell division protein FtsZ

Gabriella M. Nepomuceno, Katie M. Chan, Valerie Huynh, Kevin S. Martin, Jared T. Moore, Terrence E. Obrien, Luiz A E Pollo, Francisco J. Sarabia, Clarissa Tadeus, Zi Yao, David E. Anderson, James B. Ames, Jared T. Shaw

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

The bacterial cell division protein FtsZ is one of many potential targets for the development of novel antibiotics. Recently, zantrin Z3 was shown to be a cross-species inhibitor of FtsZ; however, its specific interactions with the protein are still unknown. Herein we report the synthesis of analogues that contain a more tractable core structure and an analogue with single-digit micromolar inhibition of FtsZs GTPase activity, which represents the most potent inhibitor of Escherichia coli FtsZ reported to date. In addition, the zantrin Z3 core has been converted to two potential photo-cross-linking reagents for proteomic studies that could shed light on the molecular interactions between FtsZ and molecules related to zantrin Z3.

Original languageEnglish (US)
Pages (from-to)308-312
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume6
Issue number3
DOIs
StatePublished - Mar 12 2015

Keywords

  • bacterial cell division
  • FtsZ
  • SAR
  • zantrin Z3

ASJC Scopus subject areas

  • Organic Chemistry
  • Drug Discovery
  • Biochemistry

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    Nepomuceno, G. M., Chan, K. M., Huynh, V., Martin, K. S., Moore, J. T., Obrien, T. E., Pollo, L. A. E., Sarabia, F. J., Tadeus, C., Yao, Z., Anderson, D. E., Ames, J. B., & Shaw, J. T. (2015). Synthesis and evaluation of quinazolines as inhibitors of the bacterial cell division protein FtsZ. ACS Medicinal Chemistry Letters, 6(3), 308-312. https://doi.org/10.1021/ml500497s