Molecular modification proposal: analysis of physicochemical, pharmacokinetic and toxicological parameters “in silico” of barbituric drugs
Autor(a) principal: | |
---|---|
Data de Publicação: | 2022 |
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/35680 |
Resumo: | This research aimed to propose molecular modifications and compare the characteristics of three barbiturate drugs and their analogues developed in silico through procedures and computational techniques using free programs. Barbiturates were the class chosen for this study, the selected drugs were: Phenobarbital, Pentobarbital and Amobarbital, being modified through simulations in silico. Three analogues were proposed, being analyzed and compared with the prototypes, using the free programs, Marvinsketch, where it was possible to evaluate parameters such as: Log P, hydrogen donors/acceptors and Van Der Walls Surface. In PreADMET, parameters such as BHE, HIA, Caco-2, MDCK, CYP-3A4, Ames Test, Carcinogenicity (Rats) and hERG Risk were obtained. Through the Osiris Property Explorer, the following parameters were evaluated: Mutagenicity, tumorigenicity, irritability, reproductive effect, solubility, molecular weight, polarity, druglikeness and Drug-Score. With the results obtained in PreADMET referring to BHE, the analogues BBT-F and BBT-A obtained better results, while the BBT-P had a worsening in the result. In relation to HIA, the values proved to be satisfactory, exhibiting good intestinal absorption. As for toxicity, the Ames test was verified, where all molecules were mutagenic. With the results obtained in Osiris, all the prototype drugs proved to be mutagenic, while in the analogues, only BBT-P showed mutagenicity. As for tumorigenicity, the prototype drugs remained at medium to high risk, while analogue drugs all showed non-tumorigenic results. Therefore, it is concluded that it was possible to make a preliminary, fast and low-cost analysis, helping in the research of new drugs through computational tools. |
id |
UNIFEI_1ea526904b710618d29013b34b133bd1 |
---|---|
oai_identifier_str |
oai:ojs.pkp.sfu.ca:article/35680 |
network_acronym_str |
UNIFEI |
network_name_str |
Research, Society and Development |
repository_id_str |
|
spelling |
Molecular modification proposal: analysis of physicochemical, pharmacokinetic and toxicological parameters “in silico” of barbituric drugs Propuesta de modificación molecular: análisis de parámetros fisicoquímicos, farmacocinéticos y toxicológicos “in silico” de medicamentos barbitúricos Proposta de modificação molecular: análise de parâmetros físico-químicos, farmacocinéticos e toxicológicos “in sílico” de fármacos barbitúricosTécnicas computacionaisAnálogosMoléculaToxicidade.Técnicas computacionalesAnálogosMoléculaToxicidade.Computational techniquesAnaloguesMoleculeToxicity.This research aimed to propose molecular modifications and compare the characteristics of three barbiturate drugs and their analogues developed in silico through procedures and computational techniques using free programs. Barbiturates were the class chosen for this study, the selected drugs were: Phenobarbital, Pentobarbital and Amobarbital, being modified through simulations in silico. Three analogues were proposed, being analyzed and compared with the prototypes, using the free programs, Marvinsketch, where it was possible to evaluate parameters such as: Log P, hydrogen donors/acceptors and Van Der Walls Surface. In PreADMET, parameters such as BHE, HIA, Caco-2, MDCK, CYP-3A4, Ames Test, Carcinogenicity (Rats) and hERG Risk were obtained. Through the Osiris Property Explorer, the following parameters were evaluated: Mutagenicity, tumorigenicity, irritability, reproductive effect, solubility, molecular weight, polarity, druglikeness and Drug-Score. With the results obtained in PreADMET referring to BHE, the analogues BBT-F and BBT-A obtained better results, while the BBT-P had a worsening in the result. In relation to HIA, the values proved to be satisfactory, exhibiting good intestinal absorption. As for toxicity, the Ames test was verified, where all molecules were mutagenic. With the results obtained in Osiris, all the prototype drugs proved to be mutagenic, while in the analogues, only BBT-P showed mutagenicity. As for tumorigenicity, the prototype drugs remained at medium to high risk, while analogue drugs all showed non-tumorigenic results. Therefore, it is concluded that it was possible to make a preliminary, fast and low-cost analysis, helping in the research of new drugs through computational tools.Este trabajo tuvo como objetivo proponer modificaciones moleculares y comparar las características de tres fármacos barbitúricos y sus análogos desarrollos in silico a través de procedimientos y técnicas computacionales utilizando programas libres. Los barbitúricos fueron la clase escogida para este estudio, los fármacos seleccionados fueron: Fenobarbital, Pentobarbital y Amobarbital, siendo modificados en simulaciones in silico. Se propusieron tres análogos, siendo analizados y comparados con los prototipos, utilizando programas libres, Marvinsketch, evaluó parámetros como: Log P, donantes/aceptores de hidrógeno y Superficie de Van Der Walls. En PreADMET se obtuvieron parámetros como BHE, HIA, Caco-2, MDCK, CYP-3A4, Prueba de Ames, Carcinogenicidad (Ratas) y Riesgo hERG. Usando el Osiris Property Explorer, se evaluaron los siguientes parámetros: Mutagenicidad, tumorigenicidad, irritabilidad, reproducción, solubilidad, peso molecular, polaridad, druglikness y Drug-Score. Los resultados obtenidos en PreADMET referidos a BHE, los análogos BBT-F y BBT-A obtuvieron mejores resultados, mientras que BBT-P tuvo peor resultado. En relación a HIA, los valores fueron satisfactorios, con buena absorción intestinal. En la toxicidad, se verificó la prueba de Ames, donde todas las moléculas resultaron mutagénicas. Con los resultados obtenidos en Osiris, todos los fármacos prototipo demostraron ser mutagénicos, mientras que en los análogos, solo BBT-P mostró mutagenicidad. En cuanto a la tumorigenicidad, los fármacos prototipo permanecieron en un riesgo medio a alto, mientras que todos los fármacos análogos mostraron resultados no tumorigénicos. Por lo tanto, se concluye que fue posible realizar un análisis preliminar, rápido y de bajo costo, ayudando en la investigación de nuevos fármacos a través de herramientas computacionales. Este trabalho teve como objetivo propor modificações moleculares e comparar as características de três fármacos barbitúricos e de seus análogos desenvolvidos in sílico através de procedimentos e técnicas computacionais utilizando programas gratuitos. Os barbitúricos foram a classe escolhida para esse estudo, os fármacos selecionados foram: Fenobarbital, Pentobarbital e Amobarbital, sendo modificados através de simulações in sílico. Foram propostos três análogos, sendo analisados e comparados com os protótipos, utilizando os programas gratuitos, Marvinsketch, onde foi possível avaliar parâmetros como: Log P, doadores/aceptores de hidrogênio e Superfície de Van Der Walls. No PreADMET se obteve parâmetros como BHE, HIA, Caco-2, MDCK, CYP-3A4, Teste Ames, Carcinogenicidade (Ratos) e Risco hERG. Através do Osiris Property Explorer, foi avaliado os seguintes parâmetros: Mutagenicidade, tumorigenicidade, irritabilidade, efeito reprodutivo, solubilidade, peso molecular, polaridade, druglikeness e Drug-Score. Com os resultados obtidos no PreADMET referentes a BHE, os análogos BBT-F e BBT-A obtiveram melhores resultados, enquanto o BBT-P houve piora no resultado. Em relação ao HIA, os valores se mostraram satisfatórios, apresentando uma boa absorção intestinal. Quanto a toxicidade, foi verificado o teste de Ames, onde todas as moléculas se apresentaram mutagênicas. Com os resultados obtidos no Osíris, todos os fármacos protótipos se mostraram mutagênicos, enquanto nos análogos, apenas o BBT-P apresentou mutagenicidade. Quanto a tumorigenicidade, os fármacos protótipos se mantiveram em risco médio a elevado, enquanto os fármacos análogos, todos apresentaram resultados não tumorigênicos. Portanto, conclui-se que foi possível fazer uma análise preliminar, rápida e de baixo custo, auxiliando na pesquisa de novos fármacos através de ferramentas computacionais.Research, Society and Development2022-10-14info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://rsdjournal.org/index.php/rsd/article/view/3568010.33448/rsd-v11i13.35680Research, Society and Development; Vol. 11 No. 13; e5291111335680Research, Society and Development; Vol. 11 Núm. 13; e5291111335680Research, Society and Development; v. 11 n. 13; e52911113356802525-3409reponame:Research, Society and Developmentinstname:Universidade Federal de Itajubá (UNIFEI)instacron:UNIFEIporhttps://rsdjournal.org/index.php/rsd/article/view/35680/29956Copyright (c) 2022 Henrique Hidelbrando Mendes Silva; Matheus Henrique Pereira Alves; Renan José Sousa Gonçalves ; Nathalia de Aguiar Pereira; Cristiano Ribeiro Gonçalves Affonsohttps://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccess Silva, Henrique Hidelbrando Mendes Alves, Matheus Henrique PereiraGonçalves , Renan José Sousa Pereira, Nathalia de Aguiar Affonso, Cristiano Ribeiro Gonçalves 2022-10-17T13:43:46Zoai:ojs.pkp.sfu.ca:article/35680Revistahttps://rsdjournal.org/index.php/rsd/indexPUBhttps://rsdjournal.org/index.php/rsd/oairsd.articles@gmail.com2525-34092525-3409opendoar:2024-01-17T09:50:30.608294Research, Society and Development - Universidade Federal de Itajubá (UNIFEI)false |
dc.title.none.fl_str_mv |
Molecular modification proposal: analysis of physicochemical, pharmacokinetic and toxicological parameters “in silico” of barbituric drugs Propuesta de modificación molecular: análisis de parámetros fisicoquímicos, farmacocinéticos y toxicológicos “in silico” de medicamentos barbitúricos Proposta de modificação molecular: análise de parâmetros físico-químicos, farmacocinéticos e toxicológicos “in sílico” de fármacos barbitúricos |
title |
Molecular modification proposal: analysis of physicochemical, pharmacokinetic and toxicological parameters “in silico” of barbituric drugs |
spellingShingle |
Molecular modification proposal: analysis of physicochemical, pharmacokinetic and toxicological parameters “in silico” of barbituric drugs Silva, Henrique Hidelbrando Mendes Técnicas computacionais Análogos Molécula Toxicidade. Técnicas computacionales Análogos Molécula Toxicidade. Computational techniques Analogues Molecule Toxicity. |
title_short |
Molecular modification proposal: analysis of physicochemical, pharmacokinetic and toxicological parameters “in silico” of barbituric drugs |
title_full |
Molecular modification proposal: analysis of physicochemical, pharmacokinetic and toxicological parameters “in silico” of barbituric drugs |
title_fullStr |
Molecular modification proposal: analysis of physicochemical, pharmacokinetic and toxicological parameters “in silico” of barbituric drugs |
title_full_unstemmed |
Molecular modification proposal: analysis of physicochemical, pharmacokinetic and toxicological parameters “in silico” of barbituric drugs |
title_sort |
Molecular modification proposal: analysis of physicochemical, pharmacokinetic and toxicological parameters “in silico” of barbituric drugs |
author |
Silva, Henrique Hidelbrando Mendes |
author_facet |
Silva, Henrique Hidelbrando Mendes Alves, Matheus Henrique Pereira Gonçalves , Renan José Sousa Pereira, Nathalia de Aguiar Affonso, Cristiano Ribeiro Gonçalves |
author_role |
author |
author2 |
Alves, Matheus Henrique Pereira Gonçalves , Renan José Sousa Pereira, Nathalia de Aguiar Affonso, Cristiano Ribeiro Gonçalves |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
Silva, Henrique Hidelbrando Mendes Alves, Matheus Henrique Pereira Gonçalves , Renan José Sousa Pereira, Nathalia de Aguiar Affonso, Cristiano Ribeiro Gonçalves |
dc.subject.por.fl_str_mv |
Técnicas computacionais Análogos Molécula Toxicidade. Técnicas computacionales Análogos Molécula Toxicidade. Computational techniques Analogues Molecule Toxicity. |
topic |
Técnicas computacionais Análogos Molécula Toxicidade. Técnicas computacionales Análogos Molécula Toxicidade. Computational techniques Analogues Molecule Toxicity. |
description |
This research aimed to propose molecular modifications and compare the characteristics of three barbiturate drugs and their analogues developed in silico through procedures and computational techniques using free programs. Barbiturates were the class chosen for this study, the selected drugs were: Phenobarbital, Pentobarbital and Amobarbital, being modified through simulations in silico. Three analogues were proposed, being analyzed and compared with the prototypes, using the free programs, Marvinsketch, where it was possible to evaluate parameters such as: Log P, hydrogen donors/acceptors and Van Der Walls Surface. In PreADMET, parameters such as BHE, HIA, Caco-2, MDCK, CYP-3A4, Ames Test, Carcinogenicity (Rats) and hERG Risk were obtained. Through the Osiris Property Explorer, the following parameters were evaluated: Mutagenicity, tumorigenicity, irritability, reproductive effect, solubility, molecular weight, polarity, druglikeness and Drug-Score. With the results obtained in PreADMET referring to BHE, the analogues BBT-F and BBT-A obtained better results, while the BBT-P had a worsening in the result. In relation to HIA, the values proved to be satisfactory, exhibiting good intestinal absorption. As for toxicity, the Ames test was verified, where all molecules were mutagenic. With the results obtained in Osiris, all the prototype drugs proved to be mutagenic, while in the analogues, only BBT-P showed mutagenicity. As for tumorigenicity, the prototype drugs remained at medium to high risk, while analogue drugs all showed non-tumorigenic results. Therefore, it is concluded that it was possible to make a preliminary, fast and low-cost analysis, helping in the research of new drugs through computational tools. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-10-14 |
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/35680 10.33448/rsd-v11i13.35680 |
url |
https://rsdjournal.org/index.php/rsd/article/view/35680 |
identifier_str_mv |
10.33448/rsd-v11i13.35680 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.none.fl_str_mv |
https://rsdjournal.org/index.php/rsd/article/view/35680/29956 |
dc.rights.driver.fl_str_mv |
https://creativecommons.org/licenses/by/4.0 info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
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. 11 No. 13; e5291111335680 Research, Society and Development; Vol. 11 Núm. 13; e5291111335680 Research, Society and Development; v. 11 n. 13; e5291111335680 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 |
_version_ |
1797052725271199744 |