Facile Access to Structurally Diverse Antimalarial Indoles Using a One-Pot A3 Coupling and Domino Cyclization Approach

Detalhes bibliográficos
Autor(a) principal: da Silva, Gustavo
Data de Publicação: 2023
Outros Autores: 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
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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spelling 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.Global Health and Tropical Medicine (GHTM)Instituto de Higiene e Medicina Tropical (IHMT)Vector borne diseases and pathogens (VBD)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:RCAAP2024-03-11T05:41:26Zoai:run.unl.pt:10362/158923Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:57:20.813306Repositório 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 Global Health and Tropical Medicine (GHTM)
Instituto de Higiene e Medicina Tropical (IHMT)
Vector borne diseases and pathogens (VBD)
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
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dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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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
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