Structure-Activity Relationship for the Oxadiazole Class of Antibacterials

Autores
Boudreau, Marc A.; Ding, Derong; Meisel, Jayda E.; Janardhanan, Jeshina; Spink, Edward; Peng, Zhihong; Qian, Yuanyuan; Yamaguchi, Takao; Testero, Sebastian Andres; O'Daniel, Peter I.; Leemans, Erika; Lastochkin, Elena; Song, Wei; Schroeder, Valerie A.; Wolter, William R.; Suckow, Mark A.; Mobashery, Shahriar; Chang, Mayland
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
A structure-activity relationship (SAR) for the oxadiazole class of antibacterials was evaluated by syntheses of 72 analogs and determination of the minimal-inhibitory concentrations (MICs) against the ESKAPE panel of bacteria. Selected compounds were further evaluated for in vitro toxicity, plasma protein binding, pharmacokinetics (PK), and a mouse model of methicillin-resistant Staphylococcus aureus (MRSA) infection. Oxadiazole 72c shows potent in vitro antibacterial activity, exhibits low clearance, a high volume of distribution, and 41% oral bioavailability, and shows efficacy in mouse models of MRSA infection.
Fil: Boudreau, Marc A.. University of Notre Dame; Estados Unidos
Fil: Ding, Derong. University of Notre Dame; Estados Unidos
Fil: Meisel, Jayda E.. University of Notre Dame; Estados Unidos
Fil: Janardhanan, Jeshina. University of Notre Dame; Estados Unidos
Fil: Spink, Edward. University of Notre Dame; Estados Unidos
Fil: Peng, Zhihong. University of Notre Dame; Estados Unidos
Fil: Qian, Yuanyuan. University of Notre Dame; Estados Unidos
Fil: Yamaguchi, Takao. University of Notre Dame; Estados Unidos
Fil: Testero, Sebastian Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina. University of Notre Dame; Estados Unidos
Fil: O'Daniel, Peter I.. University of Notre Dame; Estados Unidos
Fil: Leemans, Erika. University of Notre Dame; Estados Unidos
Fil: Lastochkin, Elena. University of Notre Dame; Estados Unidos
Fil: Song, Wei. University of Notre Dame; Estados Unidos
Fil: Schroeder, Valerie A.. University of Notre Dame; Estados Unidos
Fil: Wolter, William R.. University of Notre Dame; Estados Unidos
Fil: Suckow, Mark A.. University of Notre Dame; Estados Unidos
Fil: Mobashery, Shahriar. University of Notre Dame; Estados Unidos
Fil: Chang, Mayland. University of Notre Dame; Estados Unidos
Materia
ANTIBACTERIALS
OXADIAZOLES
PENICILLIN-BINDING PROTEINS
STRUCTURE-ACTIVITY RELATIONSHIP
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/117105
Acceder
id CONICETDig_556a3e74c4a4018196105bc83eab251b
oai_identifier_str oai:ri.conicet.gov.ar:11336/117105
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Structure-Activity Relationship for the Oxadiazole Class of AntibacterialsBoudreau, Marc A.Ding, DerongMeisel, Jayda E.Janardhanan, JeshinaSpink, EdwardPeng, ZhihongQian, YuanyuanYamaguchi, TakaoTestero, Sebastian AndresO'Daniel, Peter I.Leemans, ErikaLastochkin, ElenaSong, WeiSchroeder, Valerie A.Wolter, William R.Suckow, Mark A.Mobashery, ShahriarChang, MaylandANTIBACTERIALSOXADIAZOLESPENICILLIN-BINDING PROTEINSSTRUCTURE-ACTIVITY RELATIONSHIPhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1A structure-activity relationship (SAR) for the oxadiazole class of antibacterials was evaluated by syntheses of 72 analogs and determination of the minimal-inhibitory concentrations (MICs) against the ESKAPE panel of bacteria. Selected compounds were further evaluated for in vitro toxicity, plasma protein binding, pharmacokinetics (PK), and a mouse model of methicillin-resistant Staphylococcus aureus (MRSA) infection. Oxadiazole 72c shows potent in vitro antibacterial activity, exhibits low clearance, a high volume of distribution, and 41% oral bioavailability, and shows efficacy in mouse models of MRSA infection.Fil: Boudreau, Marc A.. University of Notre Dame; Estados UnidosFil: Ding, Derong. University of Notre Dame; Estados UnidosFil: Meisel, Jayda E.. University of Notre Dame; Estados UnidosFil: Janardhanan, Jeshina. University of Notre Dame; Estados UnidosFil: Spink, Edward. University of Notre Dame; Estados UnidosFil: Peng, Zhihong. University of Notre Dame; Estados UnidosFil: Qian, Yuanyuan. University of Notre Dame; Estados UnidosFil: Yamaguchi, Takao. University of Notre Dame; Estados UnidosFil: Testero, Sebastian Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina. University of Notre Dame; Estados UnidosFil: O'Daniel, Peter I.. University of Notre Dame; Estados UnidosFil: Leemans, Erika. University of Notre Dame; Estados UnidosFil: Lastochkin, Elena. University of Notre Dame; Estados UnidosFil: Song, Wei. University of Notre Dame; Estados UnidosFil: Schroeder, Valerie A.. University of Notre Dame; Estados UnidosFil: Wolter, William R.. University of Notre Dame; Estados UnidosFil: Suckow, Mark A.. University of Notre Dame; Estados UnidosFil: Mobashery, Shahriar. University of Notre Dame; Estados UnidosFil: Chang, Mayland. University of Notre Dame; Estados UnidosAmerican Chemical Society2020-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/117105Boudreau, Marc A.; Ding, Derong; Meisel, Jayda E.; Janardhanan, Jeshina; Spink, Edward; et al.; Structure-Activity Relationship for the Oxadiazole Class of Antibacterials; American Chemical Society; ACS Medicinal Chemistry Letters; 11; 3; 3-2020; 322-3261948-5875CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/10.1021/acsmedchemlett.9b00379info:eu-repo/semantics/altIdentifier/doi/10.1021/acsmedchemlett.9b00379info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:37:50Zoai:ri.conicet.gov.ar:11336/117105instacron: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 09:37:50.568CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Structure-Activity Relationship for the Oxadiazole Class of Antibacterials
title Structure-Activity Relationship for the Oxadiazole Class of Antibacterials
spellingShingle Structure-Activity Relationship for the Oxadiazole Class of Antibacterials
Boudreau, Marc A.
ANTIBACTERIALS
OXADIAZOLES
PENICILLIN-BINDING PROTEINS
STRUCTURE-ACTIVITY RELATIONSHIP
title_short Structure-Activity Relationship for the Oxadiazole Class of Antibacterials
title_full Structure-Activity Relationship for the Oxadiazole Class of Antibacterials
title_fullStr Structure-Activity Relationship for the Oxadiazole Class of Antibacterials
title_full_unstemmed Structure-Activity Relationship for the Oxadiazole Class of Antibacterials
title_sort Structure-Activity Relationship for the Oxadiazole Class of Antibacterials
dc.creator.none.fl_str_mv Boudreau, Marc A.
Ding, Derong
Meisel, Jayda E.
Janardhanan, Jeshina
Spink, Edward
Peng, Zhihong
Qian, Yuanyuan
Yamaguchi, Takao
Testero, Sebastian Andres
O'Daniel, Peter I.
Leemans, Erika
Lastochkin, Elena
Song, Wei
Schroeder, Valerie A.
Wolter, William R.
Suckow, Mark A.
Mobashery, Shahriar
Chang, Mayland
author Boudreau, Marc A.
author_facet Boudreau, Marc A.
Ding, Derong
Meisel, Jayda E.
Janardhanan, Jeshina
Spink, Edward
Peng, Zhihong
Qian, Yuanyuan
Yamaguchi, Takao
Testero, Sebastian Andres
O'Daniel, Peter I.
Leemans, Erika
Lastochkin, Elena
Song, Wei
Schroeder, Valerie A.
Wolter, William R.
Suckow, Mark A.
Mobashery, Shahriar
Chang, Mayland
author_role author
author2 Ding, Derong
Meisel, Jayda E.
Janardhanan, Jeshina
Spink, Edward
Peng, Zhihong
Qian, Yuanyuan
Yamaguchi, Takao
Testero, Sebastian Andres
O'Daniel, Peter I.
Leemans, Erika
Lastochkin, Elena
Song, Wei
Schroeder, Valerie A.
Wolter, William R.
Suckow, Mark A.
Mobashery, Shahriar
Chang, Mayland
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ANTIBACTERIALS
OXADIAZOLES
PENICILLIN-BINDING PROTEINS
STRUCTURE-ACTIVITY RELATIONSHIP
topic ANTIBACTERIALS
OXADIAZOLES
PENICILLIN-BINDING PROTEINS
STRUCTURE-ACTIVITY RELATIONSHIP
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv A structure-activity relationship (SAR) for the oxadiazole class of antibacterials was evaluated by syntheses of 72 analogs and determination of the minimal-inhibitory concentrations (MICs) against the ESKAPE panel of bacteria. Selected compounds were further evaluated for in vitro toxicity, plasma protein binding, pharmacokinetics (PK), and a mouse model of methicillin-resistant Staphylococcus aureus (MRSA) infection. Oxadiazole 72c shows potent in vitro antibacterial activity, exhibits low clearance, a high volume of distribution, and 41% oral bioavailability, and shows efficacy in mouse models of MRSA infection.
Fil: Boudreau, Marc A.. University of Notre Dame; Estados Unidos
Fil: Ding, Derong. University of Notre Dame; Estados Unidos
Fil: Meisel, Jayda E.. University of Notre Dame; Estados Unidos
Fil: Janardhanan, Jeshina. University of Notre Dame; Estados Unidos
Fil: Spink, Edward. University of Notre Dame; Estados Unidos
Fil: Peng, Zhihong. University of Notre Dame; Estados Unidos
Fil: Qian, Yuanyuan. University of Notre Dame; Estados Unidos
Fil: Yamaguchi, Takao. University of Notre Dame; Estados Unidos
Fil: Testero, Sebastian Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina. University of Notre Dame; Estados Unidos
Fil: O'Daniel, Peter I.. University of Notre Dame; Estados Unidos
Fil: Leemans, Erika. University of Notre Dame; Estados Unidos
Fil: Lastochkin, Elena. University of Notre Dame; Estados Unidos
Fil: Song, Wei. University of Notre Dame; Estados Unidos
Fil: Schroeder, Valerie A.. University of Notre Dame; Estados Unidos
Fil: Wolter, William R.. University of Notre Dame; Estados Unidos
Fil: Suckow, Mark A.. University of Notre Dame; Estados Unidos
Fil: Mobashery, Shahriar. University of Notre Dame; Estados Unidos
Fil: Chang, Mayland. University of Notre Dame; Estados Unidos
description A structure-activity relationship (SAR) for the oxadiazole class of antibacterials was evaluated by syntheses of 72 analogs and determination of the minimal-inhibitory concentrations (MICs) against the ESKAPE panel of bacteria. Selected compounds were further evaluated for in vitro toxicity, plasma protein binding, pharmacokinetics (PK), and a mouse model of methicillin-resistant Staphylococcus aureus (MRSA) infection. Oxadiazole 72c shows potent in vitro antibacterial activity, exhibits low clearance, a high volume of distribution, and 41% oral bioavailability, and shows efficacy in mouse models of MRSA infection.
publishDate 2020
dc.date.none.fl_str_mv 2020-03
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/11336/117105
Boudreau, Marc A.; Ding, Derong; Meisel, Jayda E.; Janardhanan, Jeshina; Spink, Edward; et al.; Structure-Activity Relationship for the Oxadiazole Class of Antibacterials; American Chemical Society; ACS Medicinal Chemistry Letters; 11; 3; 3-2020; 322-326
1948-5875
CONICET Digital
CONICET
url http://hdl.handle.net/11336/117105
identifier_str_mv Boudreau, Marc A.; Ding, Derong; Meisel, Jayda E.; Janardhanan, Jeshina; Spink, Edward; et al.; Structure-Activity Relationship for the Oxadiazole Class of Antibacterials; American Chemical Society; ACS Medicinal Chemistry Letters; 11; 3; 3-2020; 322-326
1948-5875
CONICET Digital
CONICET
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/10.1021/acsmedchemlett.9b00379
info:eu-repo/semantics/altIdentifier/doi/10.1021/acsmedchemlett.9b00379
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/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
_version_ 1844613193771515904
score 13.070432

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