The protein synthesis inhibitors mycalamides A and E have limited susceptibility toward the drug efflux network
- Autores
- Venturi, Veronica; Davies, Carolina; Singh, Jonathan A.; Matthews, James H.; Bellows, David S.; Northcote, Peter T.; Keyzers, Robert A.; Teesdale Spittle, Paul
- Año de publicación
- 2012
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- The mycalamides belong to a family of protein synthesis inhibitors noted for antifungal, antitumour, antiviral, immunosuppressive, and nematocidal activities. Here we report a systematic analysis of the role of drug efflux pumps in mycalamide resistance and the first isolation ofmycalamide E. In human cell lines, neither P-glycoprotein overexpression nor the use of efflux pump inhibitors significantly modulated mycalamide A toxicity in the systems tested. In Saccharomyces cerevisiae, it appears thatmycalamide A is subject to efflux by the principle mediator of xenobiotic efflux, Pdr5p alongwith the major facilitator superfamily pump Tpo1p. Mycalamide E showed a similar efflux profile. These results suggest that future drugs based on the mycalamides are likely to be valuable in situations where efflux pump?based resistance leads to failure of other chemotherapeutic approaches, although efflux may be a mediator of resistance in antifungal applications.
Fil: Venturi, Veronica. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda
Fil: Davies, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Cs.de la Salud. Instituto de Patología Experimental; Argentina. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda
Fil: Singh, Jonathan A.. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda
Fil: Matthews, James H.. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda
Fil: Bellows, David S.. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda
Fil: Northcote, Peter T.. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda
Fil: Keyzers, Robert A.. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda
Fil: Teesdale Spittle, Paul. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda - Materia
-
Mycalamide
Efflux
Pdr
Resistance - 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:11336/16714
Ver los metadatos del registro completo
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The protein synthesis inhibitors mycalamides A and E have limited susceptibility toward the drug efflux networkVenturi, VeronicaDavies, CarolinaSingh, Jonathan A.Matthews, James H.Bellows, David S.Northcote, Peter T.Keyzers, Robert A.Teesdale Spittle, PaulMycalamideEffluxPdrResistancehttps://purl.org/becyt/ford/1.7https://purl.org/becyt/ford/1The mycalamides belong to a family of protein synthesis inhibitors noted for antifungal, antitumour, antiviral, immunosuppressive, and nematocidal activities. Here we report a systematic analysis of the role of drug efflux pumps in mycalamide resistance and the first isolation ofmycalamide E. In human cell lines, neither P-glycoprotein overexpression nor the use of efflux pump inhibitors significantly modulated mycalamide A toxicity in the systems tested. In Saccharomyces cerevisiae, it appears thatmycalamide A is subject to efflux by the principle mediator of xenobiotic efflux, Pdr5p alongwith the major facilitator superfamily pump Tpo1p. Mycalamide E showed a similar efflux profile. These results suggest that future drugs based on the mycalamides are likely to be valuable in situations where efflux pump?based resistance leads to failure of other chemotherapeutic approaches, although efflux may be a mediator of resistance in antifungal applications.Fil: Venturi, Veronica. Victoria University of Wellington. Centre for Biodiscovery; Nueva ZelandaFil: Davies, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Cs.de la Salud. Instituto de Patología Experimental; Argentina. Victoria University of Wellington. Centre for Biodiscovery; Nueva ZelandaFil: Singh, Jonathan A.. Victoria University of Wellington. Centre for Biodiscovery; Nueva ZelandaFil: Matthews, James H.. Victoria University of Wellington. Centre for Biodiscovery; Nueva ZelandaFil: Bellows, David S.. Victoria University of Wellington. Centre for Biodiscovery; Nueva ZelandaFil: Northcote, Peter T.. Victoria University of Wellington. Centre for Biodiscovery; Nueva ZelandaFil: Keyzers, Robert A.. Victoria University of Wellington. Centre for Biodiscovery; Nueva ZelandaFil: Teesdale Spittle, Paul. Victoria University of Wellington. Centre for Biodiscovery; Nueva ZelandaJohn Wiley & Sons Inc2012-03-20info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/16714Venturi, Veronica; Davies, Carolina; Singh, Jonathan A.; Matthews, James H.; Bellows, David S.; et al.; The protein synthesis inhibitors mycalamides A and E have limited susceptibility toward the drug efflux network; John Wiley & Sons Inc; Journal Of Biochemical And Molecular Toxicology; 26; 3; 20-3-2012; 94-1001095-6670enginfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/jbt.20414/fullinfo:eu-repo/semantics/altIdentifier/doi/10.1002/jbt.20414info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:50:30Zoai:ri.conicet.gov.ar:11336/16714instacron: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 09:50:30.909CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
The protein synthesis inhibitors mycalamides A and E have limited susceptibility toward the drug efflux network |
title |
The protein synthesis inhibitors mycalamides A and E have limited susceptibility toward the drug efflux network |
spellingShingle |
The protein synthesis inhibitors mycalamides A and E have limited susceptibility toward the drug efflux network Venturi, Veronica Mycalamide Efflux Pdr Resistance |
title_short |
The protein synthesis inhibitors mycalamides A and E have limited susceptibility toward the drug efflux network |
title_full |
The protein synthesis inhibitors mycalamides A and E have limited susceptibility toward the drug efflux network |
title_fullStr |
The protein synthesis inhibitors mycalamides A and E have limited susceptibility toward the drug efflux network |
title_full_unstemmed |
The protein synthesis inhibitors mycalamides A and E have limited susceptibility toward the drug efflux network |
title_sort |
The protein synthesis inhibitors mycalamides A and E have limited susceptibility toward the drug efflux network |
dc.creator.none.fl_str_mv |
Venturi, Veronica Davies, Carolina Singh, Jonathan A. Matthews, James H. Bellows, David S. Northcote, Peter T. Keyzers, Robert A. Teesdale Spittle, Paul |
author |
Venturi, Veronica |
author_facet |
Venturi, Veronica Davies, Carolina Singh, Jonathan A. Matthews, James H. Bellows, David S. Northcote, Peter T. Keyzers, Robert A. Teesdale Spittle, Paul |
author_role |
author |
author2 |
Davies, Carolina Singh, Jonathan A. Matthews, James H. Bellows, David S. Northcote, Peter T. Keyzers, Robert A. Teesdale Spittle, Paul |
author2_role |
author author author author author author author |
dc.subject.none.fl_str_mv |
Mycalamide Efflux Pdr Resistance |
topic |
Mycalamide Efflux Pdr Resistance |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.7 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
The mycalamides belong to a family of protein synthesis inhibitors noted for antifungal, antitumour, antiviral, immunosuppressive, and nematocidal activities. Here we report a systematic analysis of the role of drug efflux pumps in mycalamide resistance and the first isolation ofmycalamide E. In human cell lines, neither P-glycoprotein overexpression nor the use of efflux pump inhibitors significantly modulated mycalamide A toxicity in the systems tested. In Saccharomyces cerevisiae, it appears thatmycalamide A is subject to efflux by the principle mediator of xenobiotic efflux, Pdr5p alongwith the major facilitator superfamily pump Tpo1p. Mycalamide E showed a similar efflux profile. These results suggest that future drugs based on the mycalamides are likely to be valuable in situations where efflux pump?based resistance leads to failure of other chemotherapeutic approaches, although efflux may be a mediator of resistance in antifungal applications. Fil: Venturi, Veronica. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda Fil: Davies, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Cs.de la Salud. Instituto de Patología Experimental; Argentina. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda Fil: Singh, Jonathan A.. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda Fil: Matthews, James H.. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda Fil: Bellows, David S.. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda Fil: Northcote, Peter T.. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda Fil: Keyzers, Robert A.. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda Fil: Teesdale Spittle, Paul. Victoria University of Wellington. Centre for Biodiscovery; Nueva Zelanda |
description |
The mycalamides belong to a family of protein synthesis inhibitors noted for antifungal, antitumour, antiviral, immunosuppressive, and nematocidal activities. Here we report a systematic analysis of the role of drug efflux pumps in mycalamide resistance and the first isolation ofmycalamide E. In human cell lines, neither P-glycoprotein overexpression nor the use of efflux pump inhibitors significantly modulated mycalamide A toxicity in the systems tested. In Saccharomyces cerevisiae, it appears thatmycalamide A is subject to efflux by the principle mediator of xenobiotic efflux, Pdr5p alongwith the major facilitator superfamily pump Tpo1p. Mycalamide E showed a similar efflux profile. These results suggest that future drugs based on the mycalamides are likely to be valuable in situations where efflux pump?based resistance leads to failure of other chemotherapeutic approaches, although efflux may be a mediator of resistance in antifungal applications. |
publishDate |
2012 |
dc.date.none.fl_str_mv |
2012-03-20 |
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/11336/16714 Venturi, Veronica; Davies, Carolina; Singh, Jonathan A.; Matthews, James H.; Bellows, David S.; et al.; The protein synthesis inhibitors mycalamides A and E have limited susceptibility toward the drug efflux network; John Wiley & Sons Inc; Journal Of Biochemical And Molecular Toxicology; 26; 3; 20-3-2012; 94-100 1095-6670 |
url |
http://hdl.handle.net/11336/16714 |
identifier_str_mv |
Venturi, Veronica; Davies, Carolina; Singh, Jonathan A.; Matthews, James H.; Bellows, David S.; et al.; The protein synthesis inhibitors mycalamides A and E have limited susceptibility toward the drug efflux network; John Wiley & Sons Inc; Journal Of Biochemical And Molecular Toxicology; 26; 3; 20-3-2012; 94-100 1095-6670 |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/jbt.20414/full info:eu-repo/semantics/altIdentifier/doi/10.1002/jbt.20414 |
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 |
John Wiley & Sons Inc |
publisher.none.fl_str_mv |
John Wiley & Sons Inc |
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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1844613556322959360 |
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13.070432 |