In silico ADME/T prediction of novel potential inhibitors against dengue virus
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | |
Tipo de documento: | Artigo |
Idioma: | por |
Título da fonte: | Research, Society and Development |
Texto Completo: | https://rsdjournal.org/index.php/rsd/article/view/14459 |
Resumo: | Dengue is an emerging disease with a major impact on public health, with millions of viral infections occurring annually, for which there is still no effective therapy. The present study aims to predict the physicochemical, pharmacokinetic and toxicological properties of candidates for drugs against dengue. 17 candidates for anti-dengue drugs were developed on the PubChem Sketcher V. 2.4® platform. The physical-chemical parameters were quantified on the Molinspiration® platform. Subsequently, the pharmacokinetic parameters were measured using the SwissADME® tool. Finally, the OSIRIS Property Explorer® platform was used to determine the toxicological effect of anti-dengue candidates. Compounds 8 and 14 did not violate any of the rules instituted by Lipinski. All other compounds showed more than one violation, with compounds 5, 7 and 9-11 showing up to 3 violations. As for the pharmacokinetic evaluation, of the compounds designed here only compounds 13 and 14 showed high gastrointestinal absorption. Compounds 2, 15 and 17 have at least a high-risk score for one of the toxicity factors for mutagenesis, tumorigenesis, irritating and reproductive effects. Compounds 1-4 have at least an intermediate risk score for one of the toxicity factors. All other compounds have low risk scores for one of the toxicity factors. The in silico prediction made in that study indicated that compounds 13 and 14 are the most promising for being possible anti-dengue candidates and useful for future screening in tests performed on cells and animals. |
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In silico ADME/T prediction of novel potential inhibitors against dengue virusPredicción in silico ADME/T de nuevos inhibidores potenciales contra el virus del denguePrevisão in silico ADME/T de novos inibidores potenciais contra o vírus da dengueDengueDenvIn silicoFerramentas computacionaisModelagem molecular.DengueDenvIn silicoComputational toolsMolecular modeling.DengueDenvIn silicoHerramientas computacionalesModelado molecular.Dengue is an emerging disease with a major impact on public health, with millions of viral infections occurring annually, for which there is still no effective therapy. The present study aims to predict the physicochemical, pharmacokinetic and toxicological properties of candidates for drugs against dengue. 17 candidates for anti-dengue drugs were developed on the PubChem Sketcher V. 2.4® platform. The physical-chemical parameters were quantified on the Molinspiration® platform. Subsequently, the pharmacokinetic parameters were measured using the SwissADME® tool. Finally, the OSIRIS Property Explorer® platform was used to determine the toxicological effect of anti-dengue candidates. Compounds 8 and 14 did not violate any of the rules instituted by Lipinski. All other compounds showed more than one violation, with compounds 5, 7 and 9-11 showing up to 3 violations. As for the pharmacokinetic evaluation, of the compounds designed here only compounds 13 and 14 showed high gastrointestinal absorption. Compounds 2, 15 and 17 have at least a high-risk score for one of the toxicity factors for mutagenesis, tumorigenesis, irritating and reproductive effects. Compounds 1-4 have at least an intermediate risk score for one of the toxicity factors. All other compounds have low risk scores for one of the toxicity factors. The in silico prediction made in that study indicated that compounds 13 and 14 are the most promising for being possible anti-dengue candidates and useful for future screening in tests performed on cells and animals.El dengue es una enfermedad emergente con un gran impacto en la salud pública, con millones de infecciones virales que ocurren anualmente, para las cuales aún no existe una terapia efectiva. Este estudio tiene como objetivo predecir las propiedades fisicoquímicas, farmacocinéticas y toxicológicas de candidatos a fármacos contra el dengue. Se desarrollaron 17 candidatos para medicamentos contra el dengue en la plataforma PubChem Sketcher V.2.4®. Los parámetros físico-químicos se cuantificaron en la plataforma Molinspiration®. Posteriormente, se midieron los parámetros farmacocinéticos utilizando la herramienta SwissADME®. Finalmente, se utilizó la plataforma OSIRIS Property Explorer® para determinar el efecto toxicológico de los candidatos anti-dengue. Los compuestos 8 y 14 no violaron ninguna de las reglas instituidas por Lipinski. Todos los demás compuestos mostraron más de una violación, y los compuestos 5, 7 y 9-11 mostraron hasta 3 violaciones. En cuanto a la evaluación farmacocinética, de los compuestos aquí diseñados, solo los compuestos 13 y 14 mostraron una alta absorción gastrointestinal. Los compuestos 2, 15 y 17 tienen al menos una puntuación de riesgo alta para uno de los factores de toxicidad para mutagénesis, tumorigénesis, efectos irritantes y reproductivos. Los compuestos 1-4 tienen al menos una puntuación de riesgo intermedia para uno de los factores de toxicidad. Todos los demás compuestos tienen una puntuación de riesgo baja para uno de los factores de toxicidad. La predicción in silico realizada en este estudio indicó que los compuestos 13 y 14 son los más prometedores por ser posibles candidatos anti-dengue y útiles para futuros cribados en pruebas realizadas en células y animales.A dengue é uma doença emergente com grande impacto na saúde pública, com milhões de infecções virais ocorrendo anualmente, para a qual ainda não existe uma terapia eficaz. O presente estudo tem como objetivo realizar a predição das propriedades físico-químicas, farmacocinéticas e toxicológicas de candidatos a medicamentos contra dengue. 17 candidatos a fármacos anti-dengue foram desenvolvidos na plataforma PubChem Sketcher V.2.4®. Os parâmetros físico-químicos foram quantificados na plataforma Molinspiration®. Posteriormente, os parâmetros farmacocinéticos foram medidos usando a ferramenta SwissADME®. Finalmente, a plataforma OSIRIS Property Explorer® foi usada para determinar o efeito toxicológico dos candidatos anti-dengue. Os compostos 8 e 14 não violaram nenhuma das regras instituídas por Lipinski. Todos os outros compostos mostraram mais de uma violação, com os compostos 5, 7 e 9-11 apresentando até 3 violações. Quanto à avaliação farmacocinética, dos compostos aqui desenhados apenas os compostos 13 e 14 apresentaram elevada absorção gastrointestinal. Os compostos 2, 15 e 17 têm pelo menos uma pontuação de alto risco para um dos fatores de toxicidade para mutagênese, tumorigênese, efeitos irritantes e reprodutivos. Os compostos 1-4 têm pelo menos uma pontuação de risco intermediária para um dos fatores de toxicidade. Todos os outros compostos têm pontuação de baixo risco para um os fatores de toxicidade. A previsão in silico realizada nesse estudo indicou que os compostos 13 e 14 são as mais promissoras para serem possíveis candidatas anti-dengue e úteis para futuras triagens em testes realizados em células e animais.Research, Society and Development2021-04-21info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://rsdjournal.org/index.php/rsd/article/view/1445910.33448/rsd-v10i4.14459Research, Society and Development; Vol. 10 No. 4; e53010414459Research, Society and Development; Vol. 10 Núm. 4; e53010414459Research, Society and Development; v. 10 n. 4; e530104144592525-3409reponame:Research, Society and Developmentinstname:Universidade Federal de Itajubá (UNIFEI)instacron:UNIFEIporhttps://rsdjournal.org/index.php/rsd/article/view/14459/12967Copyright (c) 2021 Jane Stefani da Mata Rodrigues; Eduardo Damasceno Costahttps://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccessRodrigues, Jane Stefani da Mata Costa, Eduardo Damasceno 2021-04-25T11:21:26Zoai:ojs.pkp.sfu.ca:article/14459Revistahttps://rsdjournal.org/index.php/rsd/indexPUBhttps://rsdjournal.org/index.php/rsd/oairsd.articles@gmail.com2525-34092525-3409opendoar:2024-01-17T09:35:35.063398Research, Society and Development - Universidade Federal de Itajubá (UNIFEI)false |
dc.title.none.fl_str_mv |
In silico ADME/T prediction of novel potential inhibitors against dengue virus Predicción in silico ADME/T de nuevos inhibidores potenciales contra el virus del dengue Previsão in silico ADME/T de novos inibidores potenciais contra o vírus da dengue |
title |
In silico ADME/T prediction of novel potential inhibitors against dengue virus |
spellingShingle |
In silico ADME/T prediction of novel potential inhibitors against dengue virus Rodrigues, Jane Stefani da Mata Dengue Denv In silico Ferramentas computacionais Modelagem molecular. Dengue Denv In silico Computational tools Molecular modeling. Dengue Denv In silico Herramientas computacionales Modelado molecular. |
title_short |
In silico ADME/T prediction of novel potential inhibitors against dengue virus |
title_full |
In silico ADME/T prediction of novel potential inhibitors against dengue virus |
title_fullStr |
In silico ADME/T prediction of novel potential inhibitors against dengue virus |
title_full_unstemmed |
In silico ADME/T prediction of novel potential inhibitors against dengue virus |
title_sort |
In silico ADME/T prediction of novel potential inhibitors against dengue virus |
author |
Rodrigues, Jane Stefani da Mata |
author_facet |
Rodrigues, Jane Stefani da Mata Costa, Eduardo Damasceno |
author_role |
author |
author2 |
Costa, Eduardo Damasceno |
author2_role |
author |
dc.contributor.author.fl_str_mv |
Rodrigues, Jane Stefani da Mata Costa, Eduardo Damasceno |
dc.subject.por.fl_str_mv |
Dengue Denv In silico Ferramentas computacionais Modelagem molecular. Dengue Denv In silico Computational tools Molecular modeling. Dengue Denv In silico Herramientas computacionales Modelado molecular. |
topic |
Dengue Denv In silico Ferramentas computacionais Modelagem molecular. Dengue Denv In silico Computational tools Molecular modeling. Dengue Denv In silico Herramientas computacionales Modelado molecular. |
description |
Dengue is an emerging disease with a major impact on public health, with millions of viral infections occurring annually, for which there is still no effective therapy. The present study aims to predict the physicochemical, pharmacokinetic and toxicological properties of candidates for drugs against dengue. 17 candidates for anti-dengue drugs were developed on the PubChem Sketcher V. 2.4® platform. The physical-chemical parameters were quantified on the Molinspiration® platform. Subsequently, the pharmacokinetic parameters were measured using the SwissADME® tool. Finally, the OSIRIS Property Explorer® platform was used to determine the toxicological effect of anti-dengue candidates. Compounds 8 and 14 did not violate any of the rules instituted by Lipinski. All other compounds showed more than one violation, with compounds 5, 7 and 9-11 showing up to 3 violations. As for the pharmacokinetic evaluation, of the compounds designed here only compounds 13 and 14 showed high gastrointestinal absorption. Compounds 2, 15 and 17 have at least a high-risk score for one of the toxicity factors for mutagenesis, tumorigenesis, irritating and reproductive effects. Compounds 1-4 have at least an intermediate risk score for one of the toxicity factors. All other compounds have low risk scores for one of the toxicity factors. The in silico prediction made in that study indicated that compounds 13 and 14 are the most promising for being possible anti-dengue candidates and useful for future screening in tests performed on cells and animals. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-04-21 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://rsdjournal.org/index.php/rsd/article/view/14459 10.33448/rsd-v10i4.14459 |
url |
https://rsdjournal.org/index.php/rsd/article/view/14459 |
identifier_str_mv |
10.33448/rsd-v10i4.14459 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.none.fl_str_mv |
https://rsdjournal.org/index.php/rsd/article/view/14459/12967 |
dc.rights.driver.fl_str_mv |
Copyright (c) 2021 Jane Stefani da Mata Rodrigues; Eduardo Damasceno Costa https://creativecommons.org/licenses/by/4.0 info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Copyright (c) 2021 Jane Stefani da Mata Rodrigues; Eduardo Damasceno Costa https://creativecommons.org/licenses/by/4.0 |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Research, Society and Development |
publisher.none.fl_str_mv |
Research, Society and Development |
dc.source.none.fl_str_mv |
Research, Society and Development; Vol. 10 No. 4; e53010414459 Research, Society and Development; Vol. 10 Núm. 4; e53010414459 Research, Society and Development; v. 10 n. 4; e53010414459 2525-3409 reponame:Research, Society and Development instname:Universidade Federal de Itajubá (UNIFEI) instacron:UNIFEI |
instname_str |
Universidade Federal de Itajubá (UNIFEI) |
instacron_str |
UNIFEI |
institution |
UNIFEI |
reponame_str |
Research, Society and Development |
collection |
Research, Society and Development |
repository.name.fl_str_mv |
Research, Society and Development - Universidade Federal de Itajubá (UNIFEI) |
repository.mail.fl_str_mv |
rsd.articles@gmail.com |
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1797052675298164736 |