Discovery of antibiotic (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one
Date
2015
Authors
Bouley, R.
Kumarasiri, M.
Peng, Z.
Otero, L.H.
Otero, L.H.
Song, W.
Suckow, M.A.
Schroeder, V.A.
Wolter, W.R.
Lastochkin, E.
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Advisors
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Journal article
Citation
Journal of the American Chemical Society, 2015; 137(5):1738-1741
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Abstract
In the face of the clinical challenge posed by resistant bacteria, the present needs for novel classes of antibiotics are genuine. In silico docking and screening, followed by chemical synthesis of a library of quinazolinones, led to the discovery of (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one (compound 2) as an antibiotic effective in vivo against methicillin-resistant Staphylococcus aureus (MRSA). This antibiotic impairs cell-wall biosynthesis as documented by functional assays, showing binding of 2 to penicillin-binding protein (PBP) 2a. We document that the antibiotic also inhibits PBP1 of S. aureus, indicating a broad targeting of structurally similar PBPs by this antibiotic. This class of antibiotics holds promise in fighting MRSA infections.
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Link to a related website: http://europepmc.org/articles/pmc4607046?pdf=render, Open Access via Unpaywall
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Copyright 2015 American Chemical Society