Atividade antileishmania in vitro de análogos isoxazólicos clorados derivados das neolignanas veraguensina, grandisina e machilina G
Autor(a) principal: | |
---|---|
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/123456789/7651 |
Resumo: | Cutaneous leishmaniasis (CL) is the most common clinical manifestation of leishmaniasis, with social, economic, and psychological consequences, affecting approximately 1.5 million people annually. Current treatments, initially with pentavalent antimonials and, in case of first-line treatment inefficacy, pentamidine and liposomal amphotericin B, exhibit several adverse effects, such as high toxicity. Therefore, the need for new agents to treat CL is prominent. In this study, we describe the biological activity of five new chloro-isoxazole analogs inspired by the structure of tetrahydrofuran neolignans veraguensin, grandisin, and machilin G, namely 4a, 4c, 4i, 4g, and 4e. In vitro experiments assessed the anti-leishmania activity against intracellular amastigote forms of L. amazonensis and cytotoxicity with peritoneal macrophages infected with L. amazonensis. The results showed that 4e was active against amastigotes with an IC50 value similar to the control treated with amphotericin (IC50 = 2.2 ± 0.4 µM and IC50 = 2.0 ± 0.1, respectively) and with a selectivity index for amastigotes of 22.7, higher than the tested reference drugs. Keywords: amastigotes; L. amazonensis; peritoneal macrophages; isoxazole nucleus |
id |
UFMS_4f461f634cefb38eb06b6c6e3b4da7d7 |
---|---|
oai_identifier_str |
oai:repositorio.ufms.br:123456789/7651 |
network_acronym_str |
UFMS |
network_name_str |
Repositório Institucional da UFMS |
repository_id_str |
2124 |
spelling |
2023-12-02T19:34:36Z2023-12-02T19:34:36Z2023https://repositorio.ufms.br/handle/123456789/7651Cutaneous leishmaniasis (CL) is the most common clinical manifestation of leishmaniasis, with social, economic, and psychological consequences, affecting approximately 1.5 million people annually. Current treatments, initially with pentavalent antimonials and, in case of first-line treatment inefficacy, pentamidine and liposomal amphotericin B, exhibit several adverse effects, such as high toxicity. Therefore, the need for new agents to treat CL is prominent. In this study, we describe the biological activity of five new chloro-isoxazole analogs inspired by the structure of tetrahydrofuran neolignans veraguensin, grandisin, and machilin G, namely 4a, 4c, 4i, 4g, and 4e. In vitro experiments assessed the anti-leishmania activity against intracellular amastigote forms of L. amazonensis and cytotoxicity with peritoneal macrophages infected with L. amazonensis. The results showed that 4e was active against amastigotes with an IC50 value similar to the control treated with amphotericin (IC50 = 2.2 ± 0.4 µM and IC50 = 2.0 ± 0.1, respectively) and with a selectivity index for amastigotes of 22.7, higher than the tested reference drugs. Keywords: amastigotes; L. amazonensis; peritoneal macrophages; isoxazole nucleusA leishmaniose cutânea (LC) é a manifestação clínica mais comum da leishmaniose, com consequências sociais, econômicas e psicológicas, afetando cerca de 1,5 milhão de pessoas anualmente. Os tratamentos atuais, com os antimoniais pentavalentes inicialmente e em caso de ineficácia do primeiro, a pentamidina e anfotericina B lipossomal, apresentam diversos efeitos adversos como alta toxicidade. Assim, a necessidade de novos agentes para tratar a LC é proeminente. Neste trabalho, descrevemos a atividade biológica de 5 novos análogos de cloro-isoxazol inspirados na estrutura de neolignanas tetraidrofurânicas veraguensina, grandisina e machilina G, sendo eles 4a, 4c, 4i, 4g e 4e. Experimentos in vitro avaliaram a atividade antileishmania contra formas amastigotas intracelulares de L. amazonensis; e citotoxicidade com macrófagos peritoneais infectados com L. amazonensis. Os resultados mostraram que 4e foi ativo contra amastigotas com valor de IC50 semelhante ao controle tratado com anfotericina (IC50= 2,2 ± 0,4 µM e IC50= 2,0 ± 0,1, respectivamente) e com índice de seletividade para amastigotas de 22,7, superior aos medicamentos de referência testados. Palavras-chave: amastigotas; L.amazonensis; macrófagos peritoneais, núcleo isoxazol. Fundação Universidade Federal de Mato Grosso do SulUFMSCiências da SaúdeamastigotasL.amazonensismacrófagos peritoneaisnúcleo isoxazolAtividade antileishmania in vitro de análogos isoxazólicos clorados derivados das neolignanas veraguensina, grandisina e machilina Ginfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/bachelorThesisADRIANO CESAR DE MORAIS BARONIRAFAEL FRANCISCO ROSALEMinfo:eu-repo/semantics/openAccessporreponame:Repositório Institucional da UFMSinstname:Universidade Federal de Mato Grosso do Sul (UFMS)instacron:UFMSORIGINAL9360.pdf9360.pdfapplication/pdf1953356https://repositorio.ufms.br/bitstream/123456789/7651/-1/9360.pdfacb8304ffc7e9fbf5a6a98387c2470cfMD5-1123456789/76512023-12-02 15:34:36.453oai:repositorio.ufms.br:123456789/7651Repositório InstitucionalPUBhttps://repositorio.ufms.br/oai/requestri.prograd@ufms.bropendoar:21242023-12-02T19:34:36Repositório Institucional da UFMS - Universidade Federal de Mato Grosso do Sul (UFMS)false |
dc.title.pt_BR.fl_str_mv |
Atividade antileishmania in vitro de análogos isoxazólicos clorados derivados das neolignanas veraguensina, grandisina e machilina G |
title |
Atividade antileishmania in vitro de análogos isoxazólicos clorados derivados das neolignanas veraguensina, grandisina e machilina G |
spellingShingle |
Atividade antileishmania in vitro de análogos isoxazólicos clorados derivados das neolignanas veraguensina, grandisina e machilina G RAFAEL FRANCISCO ROSALEM amastigotas L.amazonensis macrófagos peritoneais núcleo isoxazol Ciências da Saúde |
title_short |
Atividade antileishmania in vitro de análogos isoxazólicos clorados derivados das neolignanas veraguensina, grandisina e machilina G |
title_full |
Atividade antileishmania in vitro de análogos isoxazólicos clorados derivados das neolignanas veraguensina, grandisina e machilina G |
title_fullStr |
Atividade antileishmania in vitro de análogos isoxazólicos clorados derivados das neolignanas veraguensina, grandisina e machilina G |
title_full_unstemmed |
Atividade antileishmania in vitro de análogos isoxazólicos clorados derivados das neolignanas veraguensina, grandisina e machilina G |
title_sort |
Atividade antileishmania in vitro de análogos isoxazólicos clorados derivados das neolignanas veraguensina, grandisina e machilina G |
author |
RAFAEL FRANCISCO ROSALEM |
author_facet |
RAFAEL FRANCISCO ROSALEM |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
ADRIANO CESAR DE MORAIS BARONI |
dc.contributor.author.fl_str_mv |
RAFAEL FRANCISCO ROSALEM |
contributor_str_mv |
ADRIANO CESAR DE MORAIS BARONI |
dc.subject.por.fl_str_mv |
amastigotas L.amazonensis macrófagos peritoneais núcleo isoxazol |
topic |
amastigotas L.amazonensis macrófagos peritoneais núcleo isoxazol Ciências da Saúde |
dc.subject.classification.pt_BR.fl_str_mv |
Ciências da Saúde |
description |
Cutaneous leishmaniasis (CL) is the most common clinical manifestation of leishmaniasis, with social, economic, and psychological consequences, affecting approximately 1.5 million people annually. Current treatments, initially with pentavalent antimonials and, in case of first-line treatment inefficacy, pentamidine and liposomal amphotericin B, exhibit several adverse effects, such as high toxicity. Therefore, the need for new agents to treat CL is prominent. In this study, we describe the biological activity of five new chloro-isoxazole analogs inspired by the structure of tetrahydrofuran neolignans veraguensin, grandisin, and machilin G, namely 4a, 4c, 4i, 4g, and 4e. In vitro experiments assessed the anti-leishmania activity against intracellular amastigote forms of L. amazonensis and cytotoxicity with peritoneal macrophages infected with L. amazonensis. The results showed that 4e was active against amastigotes with an IC50 value similar to the control treated with amphotericin (IC50 = 2.2 ± 0.4 µM and IC50 = 2.0 ± 0.1, respectively) and with a selectivity index for amastigotes of 22.7, higher than the tested reference drugs. Keywords: amastigotes; L. amazonensis; peritoneal macrophages; isoxazole nucleus |
publishDate |
2023 |
dc.date.accessioned.fl_str_mv |
2023-12-02T19:34:36Z |
dc.date.available.fl_str_mv |
2023-12-02T19:34:36Z |
dc.date.issued.fl_str_mv |
2023 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/bachelorThesis |
format |
bachelorThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufms.br/handle/123456789/7651 |
url |
https://repositorio.ufms.br/handle/123456789/7651 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Fundação Universidade Federal de Mato Grosso do Sul |
dc.publisher.initials.fl_str_mv |
UFMS |
dc.publisher.country.pt_BR.fl_str_mv |
|
publisher.none.fl_str_mv |
Fundação Universidade Federal de Mato Grosso do Sul |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFMS instname:Universidade Federal de Mato Grosso do Sul (UFMS) instacron:UFMS |
instname_str |
Universidade Federal de Mato Grosso do Sul (UFMS) |
instacron_str |
UFMS |
institution |
UFMS |
reponame_str |
Repositório Institucional da UFMS |
collection |
Repositório Institucional da UFMS |
bitstream.url.fl_str_mv |
https://repositorio.ufms.br/bitstream/123456789/7651/-1/9360.pdf |
bitstream.checksum.fl_str_mv |
acb8304ffc7e9fbf5a6a98387c2470cf |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 |
repository.name.fl_str_mv |
Repositório Institucional da UFMS - Universidade Federal de Mato Grosso do Sul (UFMS) |
repository.mail.fl_str_mv |
ri.prograd@ufms.br |
_version_ |
1807552806046924800 |