Virtual screening of low molecular weight mushrooms compounds as potential Mdm2 inhibitors.
Main Author: | |
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Publication Date: | 2013 |
Other Authors: | , |
Format: | Article |
Language: | eng |
Source: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Download full: | http://hdl.handle.net/10198/8308 |
Summary: | In some human cancer cases, the activity of p53 is inhibited by overexpressed Mdm2. Mdm2 acts as an ubiquitin ligase, resulting in p53 ubiquitination and subsequent p53 proteasomal degradation. The disruption of the Mdm2-p53 interaction using small-molecule inhibitors is recognized as a promising strategy for anticancer drug design. Mushrooms are an important source of powerful compounds with antitumor properties. In this study, we present the first virtual screening of low molecular weight compounds present in mushroom as potential Mdm2 inhibitors. A re-docking and cross-docking method was used to validate the virtual screening protocol. The steroids: ganoderic acids X (Ki=16nM), Y (Ki=22nM) and F (Ki=69nM); 5,6-epoxy-24(R)-methylcholesta-7,22-dien-3β-ol (Ki=74nM) and polyporenic acid C (Ki=59nM) stand out as the top ranked potential inhibitors of Mdm2. The docking pose of the most promising compounds were carefully analysed and the information provided shows several interesting starting points for further development of Mdm2 inhibitors. |
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Virtual screening of low molecular weight mushrooms compounds as potential Mdm2 inhibitors.MushroomsMdm2CancerDockingAutoDock VinaIn some human cancer cases, the activity of p53 is inhibited by overexpressed Mdm2. Mdm2 acts as an ubiquitin ligase, resulting in p53 ubiquitination and subsequent p53 proteasomal degradation. The disruption of the Mdm2-p53 interaction using small-molecule inhibitors is recognized as a promising strategy for anticancer drug design. Mushrooms are an important source of powerful compounds with antitumor properties. In this study, we present the first virtual screening of low molecular weight compounds present in mushroom as potential Mdm2 inhibitors. A re-docking and cross-docking method was used to validate the virtual screening protocol. The steroids: ganoderic acids X (Ki=16nM), Y (Ki=22nM) and F (Ki=69nM); 5,6-epoxy-24(R)-methylcholesta-7,22-dien-3β-ol (Ki=74nM) and polyporenic acid C (Ki=59nM) stand out as the top ranked potential inhibitors of Mdm2. The docking pose of the most promising compounds were carefully analysed and the information provided shows several interesting starting points for further development of Mdm2 inhibitors.InformaHealthcareBiblioteca Digital do IPBFroufe, Hugo J.C.Abreu, Rui M.V.Ferreira, Isabel C.F.R.2013-04-02T13:59:48Z20132013-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfapplication/pdfhttp://hdl.handle.net/10198/8308engFroufe, Hugo J.C.; Abreu, Rui M.V.; Ferreira, Isabel C.F.R. (2013). Virtual screening of low molecular weight mushrooms compounds as potential Mdm2 inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry. ISSN 1475-6374. 28:3, p. 569-5751475-636610.3109/14756366.2012.658787info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-21T10:18:09Zoai:bibliotecadigital.ipb.pt:10198/8308Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:59:06.929332Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Virtual screening of low molecular weight mushrooms compounds as potential Mdm2 inhibitors. |
title |
Virtual screening of low molecular weight mushrooms compounds as potential Mdm2 inhibitors. |
spellingShingle |
Virtual screening of low molecular weight mushrooms compounds as potential Mdm2 inhibitors. Froufe, Hugo J.C. Mushrooms Mdm2 Cancer Docking AutoDock Vina |
title_short |
Virtual screening of low molecular weight mushrooms compounds as potential Mdm2 inhibitors. |
title_full |
Virtual screening of low molecular weight mushrooms compounds as potential Mdm2 inhibitors. |
title_fullStr |
Virtual screening of low molecular weight mushrooms compounds as potential Mdm2 inhibitors. |
title_full_unstemmed |
Virtual screening of low molecular weight mushrooms compounds as potential Mdm2 inhibitors. |
title_sort |
Virtual screening of low molecular weight mushrooms compounds as potential Mdm2 inhibitors. |
author |
Froufe, Hugo J.C. |
author_facet |
Froufe, Hugo J.C. Abreu, Rui M.V. Ferreira, Isabel C.F.R. |
author_role |
author |
author2 |
Abreu, Rui M.V. Ferreira, Isabel C.F.R. |
author2_role |
author author |
dc.contributor.none.fl_str_mv |
Biblioteca Digital do IPB |
dc.contributor.author.fl_str_mv |
Froufe, Hugo J.C. Abreu, Rui M.V. Ferreira, Isabel C.F.R. |
dc.subject.por.fl_str_mv |
Mushrooms Mdm2 Cancer Docking AutoDock Vina |
topic |
Mushrooms Mdm2 Cancer Docking AutoDock Vina |
description |
In some human cancer cases, the activity of p53 is inhibited by overexpressed Mdm2. Mdm2 acts as an ubiquitin ligase, resulting in p53 ubiquitination and subsequent p53 proteasomal degradation. The disruption of the Mdm2-p53 interaction using small-molecule inhibitors is recognized as a promising strategy for anticancer drug design. Mushrooms are an important source of powerful compounds with antitumor properties. In this study, we present the first virtual screening of low molecular weight compounds present in mushroom as potential Mdm2 inhibitors. A re-docking and cross-docking method was used to validate the virtual screening protocol. The steroids: ganoderic acids X (Ki=16nM), Y (Ki=22nM) and F (Ki=69nM); 5,6-epoxy-24(R)-methylcholesta-7,22-dien-3β-ol (Ki=74nM) and polyporenic acid C (Ki=59nM) stand out as the top ranked potential inhibitors of Mdm2. The docking pose of the most promising compounds were carefully analysed and the information provided shows several interesting starting points for further development of Mdm2 inhibitors. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-04-02T13:59:48Z 2013 2013-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10198/8308 |
url |
http://hdl.handle.net/10198/8308 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Froufe, Hugo J.C.; Abreu, Rui M.V.; Ferreira, Isabel C.F.R. (2013). Virtual screening of low molecular weight mushrooms compounds as potential Mdm2 inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry. ISSN 1475-6374. 28:3, p. 569-575 1475-6366 10.3109/14756366.2012.658787 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
InformaHealthcare |
publisher.none.fl_str_mv |
InformaHealthcare |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799135213200080896 |