Molecular modeling of a phenyl-amidine class of NMDA receptor antagonists and the rational design of new triazolyl-amidine derivatives
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2013 |
| Outros Autores: | , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/36029 |
Resumo: | Luana M. S.Marins. Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta a informação no documento. |
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Abreu, Paula AlvarezCastro, Helena C.Paes-de-Carvalho, RobertoRodrigues, Carlos R.Giongo, VivecaPaixão, Izabel C. N. P.Santana, Marcos V.Ferreira, Jainne M.Caversan, Octavia M.Leão, Raquel A. C.Marins, Luana M. S.Henriques, André M.Farias, Florence M. C.Albuquerque, Magaly G.Pinheiro, Sergio2019-10-01T13:11:09Z2019-10-01T13:11:09Z2013ABREU, Paula A. et al. Molecular modeling of a phenyl-amidine class of NMDA receptor antagonists and the rational design of new triazolyl-amidine derivatives. Chemical Biology and Drug Design, v. 81, p. 185-197, 2013.1747-0277https://www.arca.fiocruz.br/handle/icict/3602910.1111/cbdd.120561747-0285Luana M. S.Marins. Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta a informação no documento.2020-10-01Universidade Federal Fluminense. Instituto de Biologia. Departamento de Biologia Celular e Molecular. Laboratório de Antibióticos, Bioquímica e Modelagem Molecular. Niterói, RJ, Brasil / Universidade Federal do Rio de Janeiro. Laboratório de Modelagem Molecular e Pesquisa em Ciências Farmacêuticas. Macaé. RJ, Brasil.Universidade Federal Fluminense. Instituto de Biologia. Departamento de Biologia Celular e Molecular. Laboratório de Antibióticos, Bioquímica e Modelagem Molecular. Niterói, RJ, Brasil.Universidade Federal Fluminense. Instituto de Biologia. Laboratório de Neurobiologia Celular. Niterói, RJ, BrasilUniversidade Federal do Rio de Janeiro. Faculdade de Farmácia. Laboratório de Modelagem Molecular & QSAR. Rio de Janeiro, RJ, Brasil.Universidade Federal Fluminense. Instituto de Biologia. Departamento de Biologia Celular e Molecular. Laboratório de Antibióticos, Bioquímica e Modelagem Molecular. Niterói, RJ, Brasil / Universidade Federal Fluminense. Instituto de Biologia. Laboratório de Virologia Molecular. Niterói, RJ, Brasil.Universidade Federal Fluminense. Instituto de Biologia. Laboratório de Virologia Molecular. Niterói, RJ, Brasil.Universidade Federal Fluminense. Instituto de Biologia. Departamento de Biologia Celular e Molecular. Laboratório de Antibióticos, Bioquímica e Modelagem Molecular. Niterói, RJ, Brasil.Universidade Federal Fluminense. Instituto de Biologia. Laboratório de Neurobiologia Celular. Niterói, RJ, BrasilUniversidade Federal Fluminense. Instituto de Biologia. Laboratório de Neurobiologia Celular. Niterói, RJ, BrasilUniversidade Federal Fluminense. Instituto de Química. Laboratório de Síntese Assimétrica. Niterói, RJ, BrasilUniversidade Federal Fluminense. Instituto de Química. Laboratório de Síntese Assimétrica. Niterói, RJ, BrasilUniversidade Federal Fluminense. Instituto de Química. Laboratório de Síntese Assimétrica. Niterói, RJ, BrasilUniversidade Federal Fluminense. Instituto de Química. Laboratório de Síntese Assimétrica. Niterói, RJ, BrasilUniversidade Federal do Rio de Janeiro. Instituto de Química. Laboratório de Modelagem Molecular. Rio de Janeiro, RJ, Brasil.Universidade Federal Fluminense. Instituto de Química. Laboratório de Síntese Assimétrica. Niterói, RJ, BrasilRecently, many efforts have been made to develop N-methyl-D-aspartic acid receptor antagonists for treating different pathological conditions such as thrombo-embolic stroke, traumatic head injury, Huntington's, Parkinson's, and Alzheimer's diseases). However, as side-effects limit the use of most antagonists, new drugs are still required. In this work, we performed a (quantitative) structure-activity relationship analysis of 17 phenyl-amidine derivatives (1a-1q), reported as N-methyl-D-aspartic acid receptor antagonists, and used this data to rationally design the triazolyl-amidines. The best (quantitative) structure-activity relationship model constructed by multiple linear regression analysis presented high data fitting (R = 0.914) was able to explain 83.6% of the biological data variance (R(2) = 0.836), presented a satisfactory internal predictive ability (Q(2) = 0.609) and contained the descriptors (E(HOMO), Ovality and cLogP). Our assays confirmed that glutamate promotes an extensive cell death in avian neurons (77%) and 2a and 2b protected the neurons from the glutamate effect (from 77% to 27% and 45%, respectively). The results of neurotoxicity and cytotoxicity on Vero cells suggested the favorable profile of 2a and 2b. Also, the molecular modeling used to predict the activity, the interaction with the receptor and the pharmacokinetic and toxicity of the triazolyl-amidines pointed them as a promising class for further exploration as N-methyl-D-aspartic acid receptor antagonists.engWileyMolecular modeling of a phenyl-amidine class of NMDA receptor antagonists and the rational design of new triazolyl-amidine derivativesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleDrug designMolecular modelingNMDA receptor antagonistsPhenyl-amidineTriazolyl-amidineinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; 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| dc.title.pt_BR.fl_str_mv |
Molecular modeling of a phenyl-amidine class of NMDA receptor antagonists and the rational design of new triazolyl-amidine derivatives |
| title |
Molecular modeling of a phenyl-amidine class of NMDA receptor antagonists and the rational design of new triazolyl-amidine derivatives |
| spellingShingle |
Molecular modeling of a phenyl-amidine class of NMDA receptor antagonists and the rational design of new triazolyl-amidine derivatives Abreu, Paula Alvarez Drug design Molecular modeling NMDA receptor antagonists Phenyl-amidine Triazolyl-amidine |
| title_short |
Molecular modeling of a phenyl-amidine class of NMDA receptor antagonists and the rational design of new triazolyl-amidine derivatives |
| title_full |
Molecular modeling of a phenyl-amidine class of NMDA receptor antagonists and the rational design of new triazolyl-amidine derivatives |
| title_fullStr |
Molecular modeling of a phenyl-amidine class of NMDA receptor antagonists and the rational design of new triazolyl-amidine derivatives |
| title_full_unstemmed |
Molecular modeling of a phenyl-amidine class of NMDA receptor antagonists and the rational design of new triazolyl-amidine derivatives |
| title_sort |
Molecular modeling of a phenyl-amidine class of NMDA receptor antagonists and the rational design of new triazolyl-amidine derivatives |
| author |
Abreu, Paula Alvarez |
| author_facet |
Abreu, Paula Alvarez Castro, Helena C. Paes-de-Carvalho, Roberto Rodrigues, Carlos R. Giongo, Viveca Paixão, Izabel C. N. P. Santana, Marcos V. Ferreira, Jainne M. Caversan, Octavia M. Leão, Raquel A. C. Marins, Luana M. S. Henriques, André M. Farias, Florence M. C. Albuquerque, Magaly G. Pinheiro, Sergio |
| author_role |
author |
| author2 |
Castro, Helena C. Paes-de-Carvalho, Roberto Rodrigues, Carlos R. Giongo, Viveca Paixão, Izabel C. N. P. Santana, Marcos V. Ferreira, Jainne M. Caversan, Octavia M. Leão, Raquel A. C. Marins, Luana M. S. Henriques, André M. Farias, Florence M. C. Albuquerque, Magaly G. Pinheiro, Sergio |
| author2_role |
author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Abreu, Paula Alvarez Castro, Helena C. Paes-de-Carvalho, Roberto Rodrigues, Carlos R. Giongo, Viveca Paixão, Izabel C. N. P. Santana, Marcos V. Ferreira, Jainne M. Caversan, Octavia M. Leão, Raquel A. C. Marins, Luana M. S. Henriques, André M. Farias, Florence M. C. Albuquerque, Magaly G. Pinheiro, Sergio |
| dc.subject.en.pt_BR.fl_str_mv |
Drug design Molecular modeling NMDA receptor antagonists Phenyl-amidine Triazolyl-amidine |
| topic |
Drug design Molecular modeling NMDA receptor antagonists Phenyl-amidine Triazolyl-amidine |
| description |
Luana M. S.Marins. Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta a informação no documento. |
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2013 |
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2013 |
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2019-10-01T13:11:09Z |
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2019-10-01T13:11:09Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
| dc.identifier.citation.fl_str_mv |
ABREU, Paula A. et al. Molecular modeling of a phenyl-amidine class of NMDA receptor antagonists and the rational design of new triazolyl-amidine derivatives. Chemical Biology and Drug Design, v. 81, p. 185-197, 2013. |
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https://www.arca.fiocruz.br/handle/icict/36029 |
| dc.identifier.issn.pt_BR.fl_str_mv |
1747-0277 |
| dc.identifier.doi.none.fl_str_mv |
10.1111/cbdd.12056 |
| dc.identifier.eissn.none.fl_str_mv |
1747-0285 |
| identifier_str_mv |
ABREU, Paula A. et al. Molecular modeling of a phenyl-amidine class of NMDA receptor antagonists and the rational design of new triazolyl-amidine derivatives. Chemical Biology and Drug Design, v. 81, p. 185-197, 2013. 1747-0277 10.1111/cbdd.12056 1747-0285 |
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eng |
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eng |
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Wiley |
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Wiley |
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