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Synthesis and Evaluation of Quinazolines as Inhibitors of the Bacterial Cell Division Protein FtsZ.

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 FtsZ's 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.

SUBMITTER: Nepomuceno GM

PROVIDER: S-EPMC4360151 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Synthesis and Evaluation of Quinazolines as Inhibitors of the Bacterial Cell Division Protein FtsZ.

Nepomuceno Gabriella M GM Chan Katie M KM Huynh Valerie V Martin Kevin S KS Moore Jared T JT O'Brien Terrence E TE Pollo Luiz A E LA Sarabia Francisco J FJ Tadeus Clarissa C Yao Zi Z Anderson David E DE Ames James B JB Shaw Jared T JT

ACS medicinal chemistry letters 20150107 3

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 FtsZ's GTPase activity, which represents the most potent inhibitor of Escherichia coli FtsZ r ...[more]

PMID: 25815151

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