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Discovery of antibiotic (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one

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dc.contributor.authorBouley, R.
dc.contributor.authorKumarasiri, M.
dc.contributor.authorPeng, Z.
dc.contributor.authorOtero, L.H.
dc.contributor.authorOtero, L.H.
dc.contributor.authorSong, W.
dc.contributor.authorSuckow, M.A.
dc.contributor.authorSchroeder, V.A.
dc.contributor.authorWolter, W.R.
dc.contributor.authorLastochkin, E.
dc.contributor.authorAntunes, N.T.
dc.contributor.authorPi, H.
dc.contributor.authorVakulenko, S.
dc.contributor.authorHermoso, J.A.
dc.contributor.authorHermoso, J.A.
dc.contributor.authorChang, M.
dc.contributor.authorMobashery, S.
dc.date.issued2015
dc.descriptionLink to a related website: http://europepmc.org/articles/pmc4607046?pdf=render, Open Access via Unpaywall
dc.description.abstractIn 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.
dc.identifier.citationJournal of the American Chemical Society, 2015; 137(5):1738-1741
dc.identifier.doi10.1021/jacs.5b00056
dc.identifier.issn0002-7863
dc.identifier.issn1520-5126
dc.identifier.urihttps://hdl.handle.net/11541.2/122618
dc.language.isoen
dc.publisherAmerican Chemical Society
dc.relation.fundingNational Institutes of Health T32GM075762
dc.relation.fundingNational Institutes of Health F31AI115851
dc.relation.fundingAmerican Chemical Society Division of Medicinal Chemistry Predoctoral Fellowship
dc.relation.fundingSpanish Ministry of Economy and Competitiveness BFU2011-25326
dc.relation.fundingGovernment of Community of Madrid S2010/BMD-2457
dc.rightsCopyright 2015 American Chemical Society
dc.source.urihttp://dx.doi.org/10.1021/jacs.5b00056
dc.subjectpenicillin-binding proteins
dc.subjectbeta-lactam antibiotics
dc.subjectresistant staphylococcus-aureus
dc.subjectno eskape
dc.subjectpathogens
dc.titleDiscovery of antibiotic (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one
dc.typeJournal article
pubs.publication-statusPublished
ror.mmsid9916100602501831

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