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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/15602
Ver los metadatos del registro completo
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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 |
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CONICET Digital (CONICET) |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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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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1844614405192417280 |
score |
13.070432 |