Petasis adducts of tryptanthrin – synthesis, biological activity evaluation and druglikeness assessment
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/107467 https://doi.org/10.1039/D1NJ02079J |
Resumo: | Tryptanthrin is a valuable tetracyclic alkaloid, which displays a wide variety of biological activities. The application of this type of scaffold as a starting material for the discovery of new drug candidates is of major importance in medicinal chemistry. In this work, we report one of the few examples of tryptanthrin-based multicomponent reaction approaches for drug discovery, and the first using the Petasis reaction. The optimized BINOL-catalyzed reaction conditions allowed the synthesis of a library of new tryptanthrin derivatives bearing considerable structural diversity. An asymmetric version was also established, achieving the desired enantiomerically pure derivative with 99% ee and 71% yield. The resulting library was screened against one Gram-positive and one Gram-negative bacteria, two yeasts, and three filamentous and four dermatophyte fungal strains with clinical relevance, with compound 5bea displaying moderate fungicidal activity. |
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Petasis adducts of tryptanthrin – synthesis, biological activity evaluation and druglikeness assessmentTryptanthrin is a valuable tetracyclic alkaloid, which displays a wide variety of biological activities. The application of this type of scaffold as a starting material for the discovery of new drug candidates is of major importance in medicinal chemistry. In this work, we report one of the few examples of tryptanthrin-based multicomponent reaction approaches for drug discovery, and the first using the Petasis reaction. The optimized BINOL-catalyzed reaction conditions allowed the synthesis of a library of new tryptanthrin derivatives bearing considerable structural diversity. An asymmetric version was also established, achieving the desired enantiomerically pure derivative with 99% ee and 71% yield. The resulting library was screened against one Gram-positive and one Gram-negative bacteria, two yeasts, and three filamentous and four dermatophyte fungal strains with clinical relevance, with compound 5bea displaying moderate fungicidal activity.Royal Society of Chemistry2021info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/107467http://hdl.handle.net/10316/107467https://doi.org/10.1039/D1NJ02079Jeng1144-05461369-9261Brandão, PedroMarques, CarolinaPinto, EugéniaPineiro, MartaBurke, Anthony J.info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-17T08:45:21Zoai:estudogeral.uc.pt:10316/107467Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:23:49.142980Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Petasis adducts of tryptanthrin – synthesis, biological activity evaluation and druglikeness assessment |
title |
Petasis adducts of tryptanthrin – synthesis, biological activity evaluation and druglikeness assessment |
spellingShingle |
Petasis adducts of tryptanthrin – synthesis, biological activity evaluation and druglikeness assessment Brandão, Pedro |
title_short |
Petasis adducts of tryptanthrin – synthesis, biological activity evaluation and druglikeness assessment |
title_full |
Petasis adducts of tryptanthrin – synthesis, biological activity evaluation and druglikeness assessment |
title_fullStr |
Petasis adducts of tryptanthrin – synthesis, biological activity evaluation and druglikeness assessment |
title_full_unstemmed |
Petasis adducts of tryptanthrin – synthesis, biological activity evaluation and druglikeness assessment |
title_sort |
Petasis adducts of tryptanthrin – synthesis, biological activity evaluation and druglikeness assessment |
author |
Brandão, Pedro |
author_facet |
Brandão, Pedro Marques, Carolina Pinto, Eugénia Pineiro, Marta Burke, Anthony J. |
author_role |
author |
author2 |
Marques, Carolina Pinto, Eugénia Pineiro, Marta Burke, Anthony J. |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
Brandão, Pedro Marques, Carolina Pinto, Eugénia Pineiro, Marta Burke, Anthony J. |
description |
Tryptanthrin is a valuable tetracyclic alkaloid, which displays a wide variety of biological activities. The application of this type of scaffold as a starting material for the discovery of new drug candidates is of major importance in medicinal chemistry. In this work, we report one of the few examples of tryptanthrin-based multicomponent reaction approaches for drug discovery, and the first using the Petasis reaction. The optimized BINOL-catalyzed reaction conditions allowed the synthesis of a library of new tryptanthrin derivatives bearing considerable structural diversity. An asymmetric version was also established, achieving the desired enantiomerically pure derivative with 99% ee and 71% yield. The resulting library was screened against one Gram-positive and one Gram-negative bacteria, two yeasts, and three filamentous and four dermatophyte fungal strains with clinical relevance, with compound 5bea displaying moderate fungicidal activity. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/107467 http://hdl.handle.net/10316/107467 https://doi.org/10.1039/D1NJ02079J |
url |
http://hdl.handle.net/10316/107467 https://doi.org/10.1039/D1NJ02079J |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1144-0546 1369-9261 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Royal Society of Chemistry |
publisher.none.fl_str_mv |
Royal Society of Chemistry |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799134124461522944 |