Structure-Activity Relationship for the Oxadiazole Class of Antibiotics
- Autores
- Spink, Edward; Ding, Derong; Peng, Zhihong; Boudreau, Marc A.; Leemans, Erika; Lastochkin, Elena; Song, Wei; Lichtenwalter, Katerina; O’Daniel, Peter I.; Testero, Sebastian Andres; Pi, Hualiang; Schroeder, Valerie A.; Wolter, William R.; Antunes, Nuno T.; Suckow, Mark A.; Vakulenko, Sergei; Chang, Mayland; Mobashery, Shahriar
- Año de publicación
- 2015
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- The structure-activity relationship (SAR) for the newly discovered oxadiazole class of antibiotics is described with evaluation of 120 derivatives of the lead structure. This class of antibiotics was discovered by in silico docking and scoring against the crystal structure of a penicillin-binding protein. They impair cell-wall biosynthesis and exhibit activities against the Gram-positive bacterium Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA) and vancomycin-resistant and linezolid-resistant S. aureus. 5-(1H-Indol-5-yl)-3-(4-(4-(trifluoromethyl)phenoxy)phenyl)-1,2,4-oxadiazole (antibiotic 75b) was efficacious in a mouse model of MRSA infection, exhibiting a long half-life, a high volume of distribution, and low clearance. This antibiotic is bactericidal and is orally bioavailable in mice. This class of antibiotics holds great promise in recourse against infections by MRSA.
Fil: Spink, Edward. University of Notre Dame-Indiana; Estados Unidos
Fil: Ding, Derong. University of Notre Dame-Indiana; Estados Unidos
Fil: Peng, Zhihong. University of Notre Dame-Indiana; Estados Unidos
Fil: Boudreau, Marc A.. University of Notre Dame-Indiana; Estados Unidos
Fil: Leemans, Erika. University of Notre Dame-Indiana; Estados Unidos
Fil: Lastochkin, Elena. University of Notre Dame-Indiana; Estados Unidos
Fil: Song, Wei. University of Notre Dame-Indiana; Estados Unidos
Fil: Lichtenwalter, Katerina. University of Notre Dame-Indiana; Estados Unidos
Fil: O’Daniel, Peter I.. University of Notre Dame-Indiana; 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-Indiana; Estados Unidos
Fil: Pi, Hualiang. 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: Antunes, Nuno T.. University of Notre Dame-Indiana; Estados Unidos
Fil: Suckow, Mark A.. University of Notre Dame-Indiana; Estados Unidos
Fil: Vakulenko, Sergei. University of Notre Dame-Indiana; Estados Unidos
Fil: Chang, Mayland. University of Notre Dame-Indiana; Estados Unidos
Fil: Mobashery, Shahriar. University of Notre Dame-Indiana; Estados Unidos - Materia
-
Antibiotics
Penicillin-Binding Proteins
Structure-Activity Relationship
Methicillin-Resistant S. Aureus (Mrsa) - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/6066
Ver los metadatos del registro completo
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Structure-Activity Relationship for the Oxadiazole Class of AntibioticsSpink, EdwardDing, DerongPeng, ZhihongBoudreau, Marc A.Leemans, ErikaLastochkin, ElenaSong, WeiLichtenwalter, KaterinaO’Daniel, Peter I.Testero, Sebastian AndresPi, HualiangSchroeder, Valerie A.Wolter, William R.Antunes, Nuno T.Suckow, Mark A.Vakulenko, SergeiChang, MaylandMobashery, ShahriarAntibioticsPenicillin-Binding ProteinsStructure-Activity RelationshipMethicillin-Resistant S. Aureus (Mrsa)https://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1The structure-activity relationship (SAR) for the newly discovered oxadiazole class of antibiotics is described with evaluation of 120 derivatives of the lead structure. This class of antibiotics was discovered by in silico docking and scoring against the crystal structure of a penicillin-binding protein. They impair cell-wall biosynthesis and exhibit activities against the Gram-positive bacterium Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA) and vancomycin-resistant and linezolid-resistant S. aureus. 5-(1H-Indol-5-yl)-3-(4-(4-(trifluoromethyl)phenoxy)phenyl)-1,2,4-oxadiazole (antibiotic 75b) was efficacious in a mouse model of MRSA infection, exhibiting a long half-life, a high volume of distribution, and low clearance. This antibiotic is bactericidal and is orally bioavailable in mice. This class of antibiotics holds great promise in recourse against infections by MRSA.Fil: Spink, Edward. University of Notre Dame-Indiana; Estados UnidosFil: Ding, Derong. University of Notre Dame-Indiana; Estados UnidosFil: Peng, Zhihong. University of Notre Dame-Indiana; Estados UnidosFil: Boudreau, Marc A.. University of Notre Dame-Indiana; Estados UnidosFil: Leemans, Erika. University of Notre Dame-Indiana; Estados UnidosFil: Lastochkin, Elena. University of Notre Dame-Indiana; Estados UnidosFil: Song, Wei. University of Notre Dame-Indiana; Estados UnidosFil: Lichtenwalter, Katerina. University of Notre Dame-Indiana; Estados UnidosFil: O’Daniel, Peter I.. University of Notre Dame-Indiana; 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-Indiana; Estados UnidosFil: Pi, Hualiang. 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: Antunes, Nuno T.. University of Notre Dame-Indiana; Estados UnidosFil: Suckow, Mark A.. University of Notre Dame-Indiana; Estados UnidosFil: Vakulenko, Sergei. University of Notre Dame-Indiana; Estados UnidosFil: 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/pdfapplication/pdfhttp://hdl.handle.net/11336/6066Spink, Edward; Ding, Derong; Peng, Zhihong; Boudreau, Marc A.; Leemans, Erika; et al.; Structure-Activity Relationship for the Oxadiazole Class of Antibiotics; American Chemical Society; Journal of Medicinal Chemistry; 58; 3; 2-2015; 1380-13890022-2623enginfo:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/abs/10.1021/jm501661finfo:eu-repo/semantics/altIdentifier/doi/10.1021/jm501661finfo:eu-repo/semantics/altIdentifier/url/https://pubmed.ncbi.nlm.nih.gov/25590813/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:51:03Zoai:ri.conicet.gov.ar:11336/6066instacron: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:34982025-09-03 09:51:03.396CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Structure-Activity Relationship for the Oxadiazole Class of Antibiotics |
| title |
Structure-Activity Relationship for the Oxadiazole Class of Antibiotics |
| spellingShingle |
Structure-Activity Relationship for the Oxadiazole Class of Antibiotics Spink, Edward Antibiotics Penicillin-Binding Proteins Structure-Activity Relationship Methicillin-Resistant S. Aureus (Mrsa) |
| title_short |
Structure-Activity Relationship for the Oxadiazole Class of Antibiotics |
| title_full |
Structure-Activity Relationship for the Oxadiazole Class of Antibiotics |
| title_fullStr |
Structure-Activity Relationship for the Oxadiazole Class of Antibiotics |
| title_full_unstemmed |
Structure-Activity Relationship for the Oxadiazole Class of Antibiotics |
| title_sort |
Structure-Activity Relationship for the Oxadiazole Class of Antibiotics |
| dc.creator.none.fl_str_mv |
Spink, Edward Ding, Derong Peng, Zhihong Boudreau, Marc A. Leemans, Erika Lastochkin, Elena Song, Wei Lichtenwalter, Katerina O’Daniel, Peter I. Testero, Sebastian Andres Pi, Hualiang Schroeder, Valerie A. Wolter, William R. Antunes, Nuno T. Suckow, Mark A. Vakulenko, Sergei Chang, Mayland Mobashery, Shahriar |
| author |
Spink, Edward |
| author_facet |
Spink, Edward Ding, Derong Peng, Zhihong Boudreau, Marc A. Leemans, Erika Lastochkin, Elena Song, Wei Lichtenwalter, Katerina O’Daniel, Peter I. Testero, Sebastian Andres Pi, Hualiang Schroeder, Valerie A. Wolter, William R. Antunes, Nuno T. Suckow, Mark A. Vakulenko, Sergei Chang, Mayland Mobashery, Shahriar |
| author_role |
author |
| author2 |
Ding, Derong Peng, Zhihong Boudreau, Marc A. Leemans, Erika Lastochkin, Elena Song, Wei Lichtenwalter, Katerina O’Daniel, Peter I. Testero, Sebastian Andres Pi, Hualiang Schroeder, Valerie A. Wolter, William R. Antunes, Nuno T. Suckow, Mark A. Vakulenko, Sergei Chang, Mayland Mobashery, Shahriar |
| 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 |
Antibiotics Penicillin-Binding Proteins Structure-Activity Relationship Methicillin-Resistant S. Aureus (Mrsa) |
| topic |
Antibiotics Penicillin-Binding Proteins Structure-Activity Relationship Methicillin-Resistant S. Aureus (Mrsa) |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.4 https://purl.org/becyt/ford/1 |
| dc.description.none.fl_txt_mv |
The structure-activity relationship (SAR) for the newly discovered oxadiazole class of antibiotics is described with evaluation of 120 derivatives of the lead structure. This class of antibiotics was discovered by in silico docking and scoring against the crystal structure of a penicillin-binding protein. They impair cell-wall biosynthesis and exhibit activities against the Gram-positive bacterium Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA) and vancomycin-resistant and linezolid-resistant S. aureus. 5-(1H-Indol-5-yl)-3-(4-(4-(trifluoromethyl)phenoxy)phenyl)-1,2,4-oxadiazole (antibiotic 75b) was efficacious in a mouse model of MRSA infection, exhibiting a long half-life, a high volume of distribution, and low clearance. This antibiotic is bactericidal and is orally bioavailable in mice. This class of antibiotics holds great promise in recourse against infections by MRSA. Fil: Spink, Edward. University of Notre Dame-Indiana; Estados Unidos Fil: Ding, Derong. University of Notre Dame-Indiana; Estados Unidos Fil: Peng, Zhihong. University of Notre Dame-Indiana; Estados Unidos Fil: Boudreau, Marc A.. University of Notre Dame-Indiana; Estados Unidos Fil: Leemans, Erika. University of Notre Dame-Indiana; Estados Unidos Fil: Lastochkin, Elena. University of Notre Dame-Indiana; Estados Unidos Fil: Song, Wei. University of Notre Dame-Indiana; Estados Unidos Fil: Lichtenwalter, Katerina. University of Notre Dame-Indiana; Estados Unidos Fil: O’Daniel, Peter I.. University of Notre Dame-Indiana; 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-Indiana; Estados Unidos Fil: Pi, Hualiang. 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: Antunes, Nuno T.. University of Notre Dame-Indiana; Estados Unidos Fil: Suckow, Mark A.. University of Notre Dame-Indiana; Estados Unidos Fil: Vakulenko, Sergei. University of Notre Dame-Indiana; Estados Unidos Fil: Chang, Mayland. University of Notre Dame-Indiana; Estados Unidos Fil: Mobashery, Shahriar. University of Notre Dame-Indiana; Estados Unidos |
| description |
The structure-activity relationship (SAR) for the newly discovered oxadiazole class of antibiotics is described with evaluation of 120 derivatives of the lead structure. This class of antibiotics was discovered by in silico docking and scoring against the crystal structure of a penicillin-binding protein. They impair cell-wall biosynthesis and exhibit activities against the Gram-positive bacterium Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA) and vancomycin-resistant and linezolid-resistant S. aureus. 5-(1H-Indol-5-yl)-3-(4-(4-(trifluoromethyl)phenoxy)phenyl)-1,2,4-oxadiazole (antibiotic 75b) was efficacious in a mouse model of MRSA infection, exhibiting a long half-life, a high volume of distribution, and low clearance. This antibiotic is bactericidal and is orally bioavailable in mice. This class of antibiotics holds great promise in recourse against infections by MRSA. |
| 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/11336/6066 Spink, Edward; Ding, Derong; Peng, Zhihong; Boudreau, Marc A.; Leemans, Erika; et al.; Structure-Activity Relationship for the Oxadiazole Class of Antibiotics; American Chemical Society; Journal of Medicinal Chemistry; 58; 3; 2-2015; 1380-1389 0022-2623 |
| url |
http://hdl.handle.net/11336/6066 |
| identifier_str_mv |
Spink, Edward; Ding, Derong; Peng, Zhihong; Boudreau, Marc A.; Leemans, Erika; et al.; Structure-Activity Relationship for the Oxadiazole Class of Antibiotics; American Chemical Society; Journal of Medicinal Chemistry; 58; 3; 2-2015; 1380-1389 0022-2623 |
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eng |
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eng |
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