Estudo da ação antitrombótica de um análogo isoxazólico derivado de neolignana tetrahidrofurânica
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Tipo de documento: | Trabalho de conclusão de curso |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFMS |
Texto Completo: | https://repositorio.ufms.br/handle/123456789/7322 |
Resumo: | Cardiovascular diseases stand as the leading global cause of mortality, being the tromboses associated with arterial diseases one of the main causes of morbidity and mortality Thrombosis can lead to arterial obstruction, compromising the blood supply and disturbing the cellular metabolism in affected areas. The treatment of cardiovascular diseases presents numerous challenges, resulting in the need for more efficacious, safe, and user-friendly medications, especially within specialized contexts. Therefore, this study aims to investigate the antithrombotic activity (antiplatelet aggregation and anticoagulant) of an isoxazole analogue derived from tetrahydrofuran neolignans (AINT 4), in an in vitro experimental model. The synthesis of AINT 4 was carried out from cycloaddition reactions between terminal acetylenes 12 and chlorooximes 13 with substitution patterns found in neolignans. The predictive analysis (in silico) of bioavailability and oral toxicity of AINT 4 was evaluated using the SwissADME® software and Osiris® Property Explorer, respectively. The evaluation of platelet aggregation was carried out by turbidimetry, with AINT 4 being evaluated in different concentrations, using different agonists such as ADP and adrenaline, while the evaluation of coagulation was carried out in plasma using a semi-automated coagulation system. Statistical analysis was performed using analysis of variance (ANOVA), complemented by the Tukey-Kramer test, with a significance level lower than 0.05. The results showed that AINT 4 significantly inhibited platelet aggregation with both ADP (mean inhibition of 22.27%) and EPI (mean inhibition of 17.47%) at the tested concentrations. Furthermore, AINT 4 exhibited a noteworthy reduction in prothrombin time. Additionally, AINT 4 has shown to have an effect on platelet activation, resulting in an average reduction of 27% in the production of reactive oxygen species (ROS). Therefore, these findings indicate the antithrombotic activity of AINT 4. |
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2023-11-29T20:52:19Z2023-11-29T20:52:19Z2023https://repositorio.ufms.br/handle/123456789/7322Cardiovascular diseases stand as the leading global cause of mortality, being the tromboses associated with arterial diseases one of the main causes of morbidity and mortality Thrombosis can lead to arterial obstruction, compromising the blood supply and disturbing the cellular metabolism in affected areas. The treatment of cardiovascular diseases presents numerous challenges, resulting in the need for more efficacious, safe, and user-friendly medications, especially within specialized contexts. Therefore, this study aims to investigate the antithrombotic activity (antiplatelet aggregation and anticoagulant) of an isoxazole analogue derived from tetrahydrofuran neolignans (AINT 4), in an in vitro experimental model. The synthesis of AINT 4 was carried out from cycloaddition reactions between terminal acetylenes 12 and chlorooximes 13 with substitution patterns found in neolignans. The predictive analysis (in silico) of bioavailability and oral toxicity of AINT 4 was evaluated using the SwissADME® software and Osiris® Property Explorer, respectively. The evaluation of platelet aggregation was carried out by turbidimetry, with AINT 4 being evaluated in different concentrations, using different agonists such as ADP and adrenaline, while the evaluation of coagulation was carried out in plasma using a semi-automated coagulation system. Statistical analysis was performed using analysis of variance (ANOVA), complemented by the Tukey-Kramer test, with a significance level lower than 0.05. The results showed that AINT 4 significantly inhibited platelet aggregation with both ADP (mean inhibition of 22.27%) and EPI (mean inhibition of 17.47%) at the tested concentrations. Furthermore, AINT 4 exhibited a noteworthy reduction in prothrombin time. Additionally, AINT 4 has shown to have an effect on platelet activation, resulting in an average reduction of 27% in the production of reactive oxygen species (ROS). Therefore, these findings indicate the antithrombotic activity of AINT 4.As principais causas de mortes no mundo são as doenças cardiovasculares, sendo a trombose associada a doenças arteriais, uma das principais causas de morbidade e mortalidade. A trombose pode levar à obstrução arterial, ocasionando déficit sanguíneo e perturbações no metabolismo celular das áreas afetadas. As dificuldades no tratamento de doenças cardiovasculares resultam na necessidade de investigar fármacos mais eficazes, seguros e com maior facilidade de uso, principalmente em um ambiente crônico. Este estudo tem como objetivo investigar a ação antitrombótica (antiagregação plaquetária e anticoagulante) de um análogo isoxazólico derivado de neolignanas tetrahidrofuranicas (AINT 4), em modelo experimental in vitro. A síntese do AINT 4 foi realizada a partir de reações de cicloadição entre acetilenos terminais 12 e clorooximas 13 com padrões de substituição encontrados nas neolignanas. A análise preditiva (in silico) de biodisponibilidade oral e toxicidade do AINT 4 foi avaliada utilizando-se o software SwissADME® e por meio do Osiris® Property Explorer, respectivamente. A toxicidade in vitro do AINT 4 foi avaliada através do ensaio de exclusão de azul de trypan em plaquetas. A avaliação da agregação plaquetária foi realizada em plasma rico em plaquetas (PRP), por turbidimetria, sendo que o AINT 4 em foi avaliado em diferentes concentrações (9,375 - 300 µM), utilizando dois diferentes agentes agregantes, adenosina difosfato (ADP) e epinefrina (EPI). A avaliação da coagulação foi realizada em plasma utilizando sistema semi-automatizado de coagulação. A análise estatística foi por análise de variância (ANOVA), complementada pelo teste de Tukey-Kramer, com nível de significância menor que 0,05. Os resultados mostraram que o AINT 4 inibiu significativamente a agregação plaquetária tanto com ADP (inibição média de 22,27%) quanto EPI (inibição média de 17,47%) nas concentrações testadas. Além disso, o AINT 4 apresentou uma diminuição significativa no tempo de protrombina (TP). Adicionalmente, o AINT 4 mostrou ter um efeito na ativação plaquetária, resultando em uma redução média de 27% na produção de espécies reativas de oxigênio (EROs). Portanto, os resultados indicam que o AINT 4 apresenta potencial ação antitrombótica.Fundação Universidade Federal de Mato Grosso do SulUFMSCiências da SaúdeDoenças cardiovascularestromboseplaquetasantiagreganteanticoagulante.Estudo da ação antitrombótica de um análogo isoxazólico derivado de neolignana tetrahidrofurânicainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/bachelorThesisEDUARDO BENEDETTI PARISOTTORAFAEL SEIJI NAKANO OTAinfo:eu-repo/semantics/openAccessporreponame:Repositório Institucional da UFMSinstname:Universidade Federal de Mato Grosso do Sul (UFMS)instacron:UFMSORIGINAL8980.pdf8980.pdfapplication/pdf2856523https://repositorio.ufms.br/bitstream/123456789/7322/-1/8980.pdf64314e5184621f8de3c61776f676fd90MD5-1123456789/73222023-11-29 16:52:19.442oai:repositorio.ufms.br:123456789/7322Repositório InstitucionalPUBhttps://repositorio.ufms.br/oai/requestri.prograd@ufms.bropendoar:21242023-11-29T20:52:19Repositório Institucional da UFMS - Universidade Federal de Mato Grosso do Sul (UFMS)false |
dc.title.pt_BR.fl_str_mv |
Estudo da ação antitrombótica de um análogo isoxazólico derivado de neolignana tetrahidrofurânica |
title |
Estudo da ação antitrombótica de um análogo isoxazólico derivado de neolignana tetrahidrofurânica |
spellingShingle |
Estudo da ação antitrombótica de um análogo isoxazólico derivado de neolignana tetrahidrofurânica RAFAEL SEIJI NAKANO OTA Doenças cardiovasculares trombose plaquetas antiagregante anticoagulante. Ciências da Saúde |
title_short |
Estudo da ação antitrombótica de um análogo isoxazólico derivado de neolignana tetrahidrofurânica |
title_full |
Estudo da ação antitrombótica de um análogo isoxazólico derivado de neolignana tetrahidrofurânica |
title_fullStr |
Estudo da ação antitrombótica de um análogo isoxazólico derivado de neolignana tetrahidrofurânica |
title_full_unstemmed |
Estudo da ação antitrombótica de um análogo isoxazólico derivado de neolignana tetrahidrofurânica |
title_sort |
Estudo da ação antitrombótica de um análogo isoxazólico derivado de neolignana tetrahidrofurânica |
author |
RAFAEL SEIJI NAKANO OTA |
author_facet |
RAFAEL SEIJI NAKANO OTA |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
EDUARDO BENEDETTI PARISOTTO |
dc.contributor.author.fl_str_mv |
RAFAEL SEIJI NAKANO OTA |
contributor_str_mv |
EDUARDO BENEDETTI PARISOTTO |
dc.subject.por.fl_str_mv |
Doenças cardiovasculares trombose plaquetas antiagregante anticoagulante. |
topic |
Doenças cardiovasculares trombose plaquetas antiagregante anticoagulante. Ciências da Saúde |
dc.subject.classification.pt_BR.fl_str_mv |
Ciências da Saúde |
description |
Cardiovascular diseases stand as the leading global cause of mortality, being the tromboses associated with arterial diseases one of the main causes of morbidity and mortality Thrombosis can lead to arterial obstruction, compromising the blood supply and disturbing the cellular metabolism in affected areas. The treatment of cardiovascular diseases presents numerous challenges, resulting in the need for more efficacious, safe, and user-friendly medications, especially within specialized contexts. Therefore, this study aims to investigate the antithrombotic activity (antiplatelet aggregation and anticoagulant) of an isoxazole analogue derived from tetrahydrofuran neolignans (AINT 4), in an in vitro experimental model. The synthesis of AINT 4 was carried out from cycloaddition reactions between terminal acetylenes 12 and chlorooximes 13 with substitution patterns found in neolignans. The predictive analysis (in silico) of bioavailability and oral toxicity of AINT 4 was evaluated using the SwissADME® software and Osiris® Property Explorer, respectively. The evaluation of platelet aggregation was carried out by turbidimetry, with AINT 4 being evaluated in different concentrations, using different agonists such as ADP and adrenaline, while the evaluation of coagulation was carried out in plasma using a semi-automated coagulation system. Statistical analysis was performed using analysis of variance (ANOVA), complemented by the Tukey-Kramer test, with a significance level lower than 0.05. The results showed that AINT 4 significantly inhibited platelet aggregation with both ADP (mean inhibition of 22.27%) and EPI (mean inhibition of 17.47%) at the tested concentrations. Furthermore, AINT 4 exhibited a noteworthy reduction in prothrombin time. Additionally, AINT 4 has shown to have an effect on platelet activation, resulting in an average reduction of 27% in the production of reactive oxygen species (ROS). Therefore, these findings indicate the antithrombotic activity of AINT 4. |
publishDate |
2023 |
dc.date.accessioned.fl_str_mv |
2023-11-29T20:52:19Z |
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2023-11-29T20:52:19Z |
dc.date.issued.fl_str_mv |
2023 |
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info:eu-repo/semantics/bachelorThesis |
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bachelorThesis |
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https://repositorio.ufms.br/handle/123456789/7322 |
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https://repositorio.ufms.br/handle/123456789/7322 |
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Fundação Universidade Federal de Mato Grosso do Sul |
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UFMS |
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Fundação Universidade Federal de Mato Grosso do Sul |
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