Will 1,2-dihydro-1,2-azaborine-based drugs resist metabolism by cytochrome P450 compound I?
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10284/7823 |
Resumo: | 1,2-dihydro-1,2-azaborine is a structural and electronic analogue of benzene which is able to occupy benzene-binding pockets in T4 lysozyme and has been proposed as suitable arene-mimicking group for biological and pharmaceutical applications. Its applicability in a biological context requires it to be able to resist modification by xenobiotic-degrading enzymes like the P450 cytochromes. Quantum chemical computations described in this work show that 1,2-dihydro-1,2-azaborine is much more prone to modification by these enzymes than benzene, unless steric crowding of the ring prevents it from reaching the active site, or otherwise only allows reaction at the less reactive C4-position. This novel heterocyclic compound is therefore expected to be of limited usefulness as an aryl bioisostere. |
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Will 1,2-dihydro-1,2-azaborine-based drugs resist metabolism by cytochrome P450 compound I?Quantum computationsDensity-functional theoryReactivityAzaborineXenobiotics1,2-dihydro-1,2-azaborine is a structural and electronic analogue of benzene which is able to occupy benzene-binding pockets in T4 lysozyme and has been proposed as suitable arene-mimicking group for biological and pharmaceutical applications. Its applicability in a biological context requires it to be able to resist modification by xenobiotic-degrading enzymes like the P450 cytochromes. Quantum chemical computations described in this work show that 1,2-dihydro-1,2-azaborine is much more prone to modification by these enzymes than benzene, unless steric crowding of the ring prevents it from reaching the active site, or otherwise only allows reaction at the less reactive C4-position. This novel heterocyclic compound is therefore expected to be of limited usefulness as an aryl bioisostere.Repositório Institucional da Universidade Fernando PessoaSilva, Pedro J.2019-09-12T08:39:27Z2016-07-01T00:00:00Z2016-07-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10284/7823engSilva, P.J. (2016). Will 1,2-dihydro-1,2-azaborine-based drugs resist metabolism by cytochrome P450 compound I? PeerJ. https://doi.org/10.7717/peerj.2299. ISSN 2167-8359.2167-835910.7717/peerj.2299info: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:RCAAP2022-09-06T02:07:11Zoai:bdigital.ufp.pt:10284/7823Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T15:44:43.834957Repositório 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 |
Will 1,2-dihydro-1,2-azaborine-based drugs resist metabolism by cytochrome P450 compound I? |
title |
Will 1,2-dihydro-1,2-azaborine-based drugs resist metabolism by cytochrome P450 compound I? |
spellingShingle |
Will 1,2-dihydro-1,2-azaborine-based drugs resist metabolism by cytochrome P450 compound I? Silva, Pedro J. Quantum computations Density-functional theory Reactivity Azaborine Xenobiotics |
title_short |
Will 1,2-dihydro-1,2-azaborine-based drugs resist metabolism by cytochrome P450 compound I? |
title_full |
Will 1,2-dihydro-1,2-azaborine-based drugs resist metabolism by cytochrome P450 compound I? |
title_fullStr |
Will 1,2-dihydro-1,2-azaborine-based drugs resist metabolism by cytochrome P450 compound I? |
title_full_unstemmed |
Will 1,2-dihydro-1,2-azaborine-based drugs resist metabolism by cytochrome P450 compound I? |
title_sort |
Will 1,2-dihydro-1,2-azaborine-based drugs resist metabolism by cytochrome P450 compound I? |
author |
Silva, Pedro J. |
author_facet |
Silva, Pedro J. |
author_role |
author |
dc.contributor.none.fl_str_mv |
Repositório Institucional da Universidade Fernando Pessoa |
dc.contributor.author.fl_str_mv |
Silva, Pedro J. |
dc.subject.por.fl_str_mv |
Quantum computations Density-functional theory Reactivity Azaborine Xenobiotics |
topic |
Quantum computations Density-functional theory Reactivity Azaborine Xenobiotics |
description |
1,2-dihydro-1,2-azaborine is a structural and electronic analogue of benzene which is able to occupy benzene-binding pockets in T4 lysozyme and has been proposed as suitable arene-mimicking group for biological and pharmaceutical applications. Its applicability in a biological context requires it to be able to resist modification by xenobiotic-degrading enzymes like the P450 cytochromes. Quantum chemical computations described in this work show that 1,2-dihydro-1,2-azaborine is much more prone to modification by these enzymes than benzene, unless steric crowding of the ring prevents it from reaching the active site, or otherwise only allows reaction at the less reactive C4-position. This novel heterocyclic compound is therefore expected to be of limited usefulness as an aryl bioisostere. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-07-01T00:00:00Z 2016-07-01T00:00:00Z 2019-09-12T08:39:27Z |
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/10284/7823 |
url |
http://hdl.handle.net/10284/7823 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Silva, P.J. (2016). Will 1,2-dihydro-1,2-azaborine-based drugs resist metabolism by cytochrome P450 compound I? PeerJ. https://doi.org/10.7717/peerj.2299. ISSN 2167-8359. 2167-8359 10.7717/peerj.2299 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
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 |
reponame_str |
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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