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

Autores
Bouley, Renee; Kumarasiri, Malika; Peng, Zhihong; Otero, Lisandro Horacio; Song, Wei; Suckow, Mark A.; Schroeder, Valerie A.; Wolter, William R.; Lastochkin, Elena; Antunes, Nuno T.; Pi, Hualiang; Vakulenko, Sergei; Hermoso, Juan Antonio; Chang, Mayland; Mobashery, Shahriar
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Bouley, Renee. University Of Notre Dame-indiana; Estados Unidos
Fil: Kumarasiri, Malika. University Of Notre Dame-indiana; Estados Unidos
Fil: Peng, Zhihong. University Of Notre Dame-indiana; Estados Unidos
Fil: Otero, Lisandro Horacio. Consejo Superior de Investigaciones Cientificas. Instituto de Quimica Fisica; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Song, Wei. University Of Notre Dame-indiana; Estados Unidos
Fil: Suckow, Mark A.. University Of Notre Dame-indiana; Estados Unidos
Fil: Schroeder, Valerie A.. University Of Notre Dame-indiana; Estados Unidos
Fil: Wolter, William R.. University Of Notre Dame-indiana; Estados Unidos
Fil: Lastochkin, Elena. University Of Notre Dame-indiana; Estados Unidos
Fil: Antunes, Nuno T.. University Of Notre Dame-indiana; Estados Unidos
Fil: Pi, Hualiang. University Of Notre Dame-indiana; Estados Unidos
Fil: Vakulenko, Sergei. University Of Notre Dame-indiana; Estados Unidos
Fil: Hermoso, Juan Antonio. Consejo Superior de Investigaciones Cientificas. Instituto de Quimica Fisica; España
Fil: Chang, Mayland. University Of Notre Dame-indiana; Estados Unidos
Fil: Mobashery, Shahriar. University Of Notre Dame-indiana; Estados Unidos
Materia
Staphylococcus Aureus (Mrsa)
Antiobiotic Resistance
Pbp2a
Quinazolinone
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/15602
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Discovery of antibiotic (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-oneBouley, ReneeKumarasiri, MalikaPeng, ZhihongOtero, Lisandro HoracioSong, WeiSuckow, Mark A.Schroeder, Valerie A.Wolter, William R.Lastochkin, ElenaAntunes, Nuno T.Pi, HualiangVakulenko, SergeiHermoso, Juan AntonioChang, MaylandMobashery, ShahriarStaphylococcus Aureus (Mrsa)Antiobiotic ResistancePbp2aQuinazolinonehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1In 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.Fil: Bouley, Renee. University Of Notre Dame-indiana; Estados UnidosFil: Kumarasiri, Malika. University Of Notre Dame-indiana; Estados UnidosFil: Peng, Zhihong. University Of Notre Dame-indiana; Estados UnidosFil: Otero, Lisandro Horacio. Consejo Superior de Investigaciones Cientificas. Instituto de Quimica Fisica; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Song, Wei. University Of Notre Dame-indiana; Estados UnidosFil: Suckow, Mark A.. University Of Notre Dame-indiana; Estados UnidosFil: Schroeder, Valerie A.. University Of Notre Dame-indiana; Estados UnidosFil: Wolter, William R.. University Of Notre Dame-indiana; Estados UnidosFil: Lastochkin, Elena. University Of Notre Dame-indiana; Estados UnidosFil: Antunes, Nuno T.. University Of Notre Dame-indiana; Estados UnidosFil: Pi, Hualiang. University Of Notre Dame-indiana; Estados UnidosFil: Vakulenko, Sergei. University Of Notre Dame-indiana; Estados UnidosFil: Hermoso, Juan Antonio. Consejo Superior de Investigaciones Cientificas. Instituto de Quimica Fisica; EspañaFil: Chang, Mayland. University Of Notre Dame-indiana; Estados UnidosFil: Mobashery, Shahriar. University Of Notre Dame-indiana; Estados UnidosAmerican Chemical Society2015-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/15602Bouley, Renee; Kumarasiri, Malika; Peng, Zhihong; Otero, Lisandro Horacio; Song, Wei; et al.; Discovery of antibiotic (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one; American Chemical Society; Journal Of The American Chemical Society; 137; 5; 2-2015; 1738-17411520-5126enginfo:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/abs/10.1021/jacs.5b00056info:eu-repo/semantics/altIdentifier/doi/10.1021/jacs.5b00056info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:38:17Zoai:ri.conicet.gov.ar:11336/15602instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:38:17.935CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Discovery of antibiotic (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one
title Discovery of antibiotic (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one
spellingShingle Discovery of antibiotic (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one
Bouley, Renee
Staphylococcus Aureus (Mrsa)
Antiobiotic Resistance
Pbp2a
Quinazolinone
title_short Discovery of antibiotic (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one
title_full Discovery of antibiotic (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one
title_fullStr Discovery of antibiotic (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one
title_full_unstemmed Discovery of antibiotic (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one
title_sort Discovery of antibiotic (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one
dc.creator.none.fl_str_mv Bouley, Renee
Kumarasiri, Malika
Peng, Zhihong
Otero, Lisandro Horacio
Song, Wei
Suckow, Mark A.
Schroeder, Valerie A.
Wolter, William R.
Lastochkin, Elena
Antunes, Nuno T.
Pi, Hualiang
Vakulenko, Sergei
Hermoso, Juan Antonio
Chang, Mayland
Mobashery, Shahriar
author Bouley, Renee
author_facet Bouley, Renee
Kumarasiri, Malika
Peng, Zhihong
Otero, Lisandro Horacio
Song, Wei
Suckow, Mark A.
Schroeder, Valerie A.
Wolter, William R.
Lastochkin, Elena
Antunes, Nuno T.
Pi, Hualiang
Vakulenko, Sergei
Hermoso, Juan Antonio
Chang, Mayland
Mobashery, Shahriar
author_role author
author2 Kumarasiri, Malika
Peng, Zhihong
Otero, Lisandro Horacio
Song, Wei
Suckow, Mark A.
Schroeder, Valerie A.
Wolter, William R.
Lastochkin, Elena
Antunes, Nuno T.
Pi, Hualiang
Vakulenko, Sergei
Hermoso, Juan Antonio
Chang, Mayland
Mobashery, Shahriar
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Staphylococcus Aureus (Mrsa)
Antiobiotic Resistance
Pbp2a
Quinazolinone
topic Staphylococcus Aureus (Mrsa)
Antiobiotic Resistance
Pbp2a
Quinazolinone
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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.
Fil: Bouley, Renee. University Of Notre Dame-indiana; Estados Unidos
Fil: Kumarasiri, Malika. University Of Notre Dame-indiana; Estados Unidos
Fil: Peng, Zhihong. University Of Notre Dame-indiana; Estados Unidos
Fil: Otero, Lisandro Horacio. Consejo Superior de Investigaciones Cientificas. Instituto de Quimica Fisica; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Song, Wei. University Of Notre Dame-indiana; Estados Unidos
Fil: Suckow, Mark A.. University Of Notre Dame-indiana; Estados Unidos
Fil: Schroeder, Valerie A.. University Of Notre Dame-indiana; Estados Unidos
Fil: Wolter, William R.. University Of Notre Dame-indiana; Estados Unidos
Fil: Lastochkin, Elena. University Of Notre Dame-indiana; Estados Unidos
Fil: Antunes, Nuno T.. University Of Notre Dame-indiana; Estados Unidos
Fil: Pi, Hualiang. University Of Notre Dame-indiana; Estados Unidos
Fil: Vakulenko, Sergei. University Of Notre Dame-indiana; Estados Unidos
Fil: Hermoso, Juan Antonio. Consejo Superior de Investigaciones Cientificas. Instituto de Quimica Fisica; España
Fil: Chang, Mayland. University Of Notre Dame-indiana; Estados Unidos
Fil: Mobashery, Shahriar. University Of Notre Dame-indiana; Estados Unidos
description 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.
publishDate 2015
dc.date.none.fl_str_mv 2015-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/15602
Bouley, Renee; Kumarasiri, Malika; Peng, Zhihong; Otero, Lisandro Horacio; Song, Wei; et al.; Discovery of antibiotic (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one; American Chemical Society; Journal Of The American Chemical Society; 137; 5; 2-2015; 1738-1741
1520-5126
url http://hdl.handle.net/11336/15602
identifier_str_mv Bouley, Renee; Kumarasiri, Malika; Peng, Zhihong; Otero, Lisandro Horacio; Song, Wei; et al.; Discovery of antibiotic (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one; American Chemical Society; Journal Of The American Chemical Society; 137; 5; 2-2015; 1738-1741
1520-5126
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/abs/10.1021/jacs.5b00056
info:eu-repo/semantics/altIdentifier/doi/10.1021/jacs.5b00056
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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