Heterocyclic electrophiles as new MurA inhibitors

Aaron Keeley, Péter Ábrányi-Balogh, Martina Hrast, Tímea Imre, Janez Ilaš, Stanislav Gobec, György M. Keserű

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Abstract

An electrophilic fragment library of small heterocycles was developed and characterized in the surrogate GSH-reactivity assay and aqueous stability test that revealed their potential as covalent warheads. Screening the library against MurA from Staphylococcus aureus (MurA SA ) and Escherichia coli (MurA EC ) identified heterocyclic fragments with significant inhibitory potency. The validated heterocyclic warhead library might be useful for developing targeted covalent inhibitors for other targets of interest with a new design strategy incorporating heterocyclic electrophiles as warheads.

Original languageEnglish
Article number1800184
JournalArchiv der Pharmazie
Volume351
Issue number12
DOIs
Publication statusPublished - Dec 2018

Keywords

  • MurA inhibitor
  • electrophilic fragment
  • fragment-based drug discovery
  • heterocycle

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery

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  • Cite this

    Keeley, A., Ábrányi-Balogh, P., Hrast, M., Imre, T., Ilaš, J., Gobec, S., & Keserű, G. M. (2018). Heterocyclic electrophiles as new MurA inhibitors. Archiv der Pharmazie, 351(12), [1800184]. https://doi.org/10.1002/ardp.201800184