Facile Access to Structurally Diverse Antimalarial Indoles Using a One-Pot A3 Coupling and Domino Cyclization Approach
Autor(a) principal: | |
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Data de Publicação: | 2023 |
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/10362/158923 |
Resumo: | Funding Information: . The authors acknowledge the financial support provided by Fundação para a Ciência e a Tecnologia (FCT Portugal) through the PhD grant research project SFRH/BD/103412/2014 and projects PTDC/MED‐QUI/30021/2017, PTDC/MED‐CAR/31322/2017 and PTDC/SAU‐TOX/32515/2017, and the research unit GHTM (UID/Multi/04413/2013 and GHTM‐UID/04413/2020). We thank MR4 for providing us with malaria parasites contributed by Andrew Talman, Robert Sinden Funding Information: The authors acknowledge the financial support provided by Fundação para a Ciência e a Tecnologia (FCT Portugal) through the PhD grant research project SFRH/BD/103412/2014 and projects PTDC/MED-QUI/30021/2017, PTDC/MED-CAR/31322/2017 and PTDC/SAU-TOX/32515/2017, and the research unit GHTM (UID/Multi/04413/2013 and GHTM-UID/04413/2020). We thank MR4 for providing us with malaria parasites contributed by Andrew Talman, Robert Sinden. Publisher Copyright: © 2023 Wiley-VCH GmbH. |
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Facile Access to Structurally Diverse Antimalarial Indoles Using a One-Pot A3 Coupling and Domino Cyclization ApproachA couplingantimalarialsindolesmulticomponent reactionsone-pot synthesisBiochemistryMolecular MedicinePharmacologyDrug DiscoveryPharmacology, Toxicology and Pharmaceutics(all)Organic ChemistryParasitologySDG 3 - Good Health and Well-beingFunding Information: . The authors acknowledge the financial support provided by Fundação para a Ciência e a Tecnologia (FCT Portugal) through the PhD grant research project SFRH/BD/103412/2014 and projects PTDC/MED‐QUI/30021/2017, PTDC/MED‐CAR/31322/2017 and PTDC/SAU‐TOX/32515/2017, and the research unit GHTM (UID/Multi/04413/2013 and GHTM‐UID/04413/2020). We thank MR4 for providing us with malaria parasites contributed by Andrew Talman, Robert Sinden Funding Information: The authors acknowledge the financial support provided by Fundação para a Ciência e a Tecnologia (FCT Portugal) through the PhD grant research project SFRH/BD/103412/2014 and projects PTDC/MED-QUI/30021/2017, PTDC/MED-CAR/31322/2017 and PTDC/SAU-TOX/32515/2017, and the research unit GHTM (UID/Multi/04413/2013 and GHTM-UID/04413/2020). We thank MR4 for providing us with malaria parasites contributed by Andrew Talman, Robert Sinden. Publisher Copyright: © 2023 Wiley-VCH GmbH.A multistep and diversity-oriented synthetic route aiming at the A3 coupling/domino cyclization of o-ethynyl anilines, aldehydes and s-amines is described. The preparation of the corresponding precursors included a series of transformations, such as haloperoxidation and Sonogashira cross-coupling reactions, amine protection, desilylation and amine reduction. Some products of the multicomponent reaction underwent further detosylation and Suzuki coupling. The resulting library of structurally diverse compounds was evaluated against blood and liver stage malaria parasites, which revealed a promising lead with sub-micromolar activity against intra-erythrocytic forms of Plasmodium falciparum. The results from this hit-to-lead optimization are hereby reported for the first time.Vector borne diseases and pathogens (VBD)Global Health and Tropical Medicine (GHTM)Instituto de Higiene e Medicina Tropical (IHMT)RUNda Silva, GustavoLuz, André F.S.Duarte, DeniseFontinha, DianaSilva, Vera L.M.Almeida Paz, Filipe A.Madureira, Ana M.Simões, SandraPrudêncio, MiguelNogueira, FátimaSilva, Artur M.S.Moreira, Rui2023-10-13T22:18:53Z2023-09-012023-09-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article5application/pdfhttp://hdl.handle.net/10362/158923eng1860-7179PURE: 71103029https://doi.org/10.1002/cmdc.202300264info: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:RCAAP2024-06-24T01:35:03Zoai:run.unl.pt:10362/158923Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-06-24T01:35:03Repositório 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 |
Facile Access to Structurally Diverse Antimalarial Indoles Using a One-Pot A3 Coupling and Domino Cyclization Approach |
title |
Facile Access to Structurally Diverse Antimalarial Indoles Using a One-Pot A3 Coupling and Domino Cyclization Approach |
spellingShingle |
Facile Access to Structurally Diverse Antimalarial Indoles Using a One-Pot A3 Coupling and Domino Cyclization Approach da Silva, Gustavo A coupling antimalarials indoles multicomponent reactions one-pot synthesis Biochemistry Molecular Medicine Pharmacology Drug Discovery Pharmacology, Toxicology and Pharmaceutics(all) Organic Chemistry Parasitology SDG 3 - Good Health and Well-being |
title_short |
Facile Access to Structurally Diverse Antimalarial Indoles Using a One-Pot A3 Coupling and Domino Cyclization Approach |
title_full |
Facile Access to Structurally Diverse Antimalarial Indoles Using a One-Pot A3 Coupling and Domino Cyclization Approach |
title_fullStr |
Facile Access to Structurally Diverse Antimalarial Indoles Using a One-Pot A3 Coupling and Domino Cyclization Approach |
title_full_unstemmed |
Facile Access to Structurally Diverse Antimalarial Indoles Using a One-Pot A3 Coupling and Domino Cyclization Approach |
title_sort |
Facile Access to Structurally Diverse Antimalarial Indoles Using a One-Pot A3 Coupling and Domino Cyclization Approach |
author |
da Silva, Gustavo |
author_facet |
da Silva, Gustavo Luz, André F.S. Duarte, Denise Fontinha, Diana Silva, Vera L.M. Almeida Paz, Filipe A. Madureira, Ana M. Simões, Sandra Prudêncio, Miguel Nogueira, Fátima Silva, Artur M.S. Moreira, Rui |
author_role |
author |
author2 |
Luz, André F.S. Duarte, Denise Fontinha, Diana Silva, Vera L.M. Almeida Paz, Filipe A. Madureira, Ana M. Simões, Sandra Prudêncio, Miguel Nogueira, Fátima Silva, Artur M.S. Moreira, Rui |
author2_role |
author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Vector borne diseases and pathogens (VBD) Global Health and Tropical Medicine (GHTM) Instituto de Higiene e Medicina Tropical (IHMT) RUN |
dc.contributor.author.fl_str_mv |
da Silva, Gustavo Luz, André F.S. Duarte, Denise Fontinha, Diana Silva, Vera L.M. Almeida Paz, Filipe A. Madureira, Ana M. Simões, Sandra Prudêncio, Miguel Nogueira, Fátima Silva, Artur M.S. Moreira, Rui |
dc.subject.por.fl_str_mv |
A coupling antimalarials indoles multicomponent reactions one-pot synthesis Biochemistry Molecular Medicine Pharmacology Drug Discovery Pharmacology, Toxicology and Pharmaceutics(all) Organic Chemistry Parasitology SDG 3 - Good Health and Well-being |
topic |
A coupling antimalarials indoles multicomponent reactions one-pot synthesis Biochemistry Molecular Medicine Pharmacology Drug Discovery Pharmacology, Toxicology and Pharmaceutics(all) Organic Chemistry Parasitology SDG 3 - Good Health and Well-being |
description |
Funding Information: . The authors acknowledge the financial support provided by Fundação para a Ciência e a Tecnologia (FCT Portugal) through the PhD grant research project SFRH/BD/103412/2014 and projects PTDC/MED‐QUI/30021/2017, PTDC/MED‐CAR/31322/2017 and PTDC/SAU‐TOX/32515/2017, and the research unit GHTM (UID/Multi/04413/2013 and GHTM‐UID/04413/2020). We thank MR4 for providing us with malaria parasites contributed by Andrew Talman, Robert Sinden Funding Information: The authors acknowledge the financial support provided by Fundação para a Ciência e a Tecnologia (FCT Portugal) through the PhD grant research project SFRH/BD/103412/2014 and projects PTDC/MED-QUI/30021/2017, PTDC/MED-CAR/31322/2017 and PTDC/SAU-TOX/32515/2017, and the research unit GHTM (UID/Multi/04413/2013 and GHTM-UID/04413/2020). We thank MR4 for providing us with malaria parasites contributed by Andrew Talman, Robert Sinden. Publisher Copyright: © 2023 Wiley-VCH GmbH. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-10-13T22:18:53Z 2023-09-01 2023-09-01T00:00:00Z |
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/10362/158923 |
url |
http://hdl.handle.net/10362/158923 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1860-7179 PURE: 71103029 https://doi.org/10.1002/cmdc.202300264 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
5 application/pdf |
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 |
mluisa.alvim@gmail.com |
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1817545961303441408 |