Studies of Potency and Efficacy of an Optimized Artemisinin-Quinoline Hybrid against Multiple Stages of the Plasmodium Life Cycle

Detalhes bibliográficos
Autor(a) principal: Quadros, Helenita C.
Data de Publicação: 2021
Outros Autores: Çapcı, Aysun, Herrmann, Lars, D’Alessandro, Sarah, Fontinha, Diana, Azevedo, Raquel, Villarreal, Wilmer, Basilico, Nicoletta, Prudêncio, Miguel, Tsogoeva, Svetlana B., Moreira, Diogo R. M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/50256
Resumo: CAPES doctoral scholarship (Finance Code 001, Brazil). S.B.T. acknowledges the Deutsche Forschungsgemeinschaft (DFG) for funding (grant number TS87/17-1; TS87/23-1, Germany) and the Bavarian State Ministry for Science, Research and Art (Germany). D.R.M.M. acknowledges CNPq (grant No. 305732/2019-6, Brazil), FAPESB (grant number APP0088/2016, Brazil), and Fiocruz/Proep (grant number IGM-002-FIO-20-2-25, Brazil). M.P. was supported by grant PTDC-SAU-INF-29550-2017 (FCT, Portugal). S.D. and N.B. were supported by the by Fondazione Cariplo (grant number 2017-0846), the Ministero dell’Istruzione, dell’Università e della Ricerca (grant number PRIN 2015.4JRJPP_004), and the Ministero degli Affari Esteri e della Cooperazione Internazionale (Progetti di grande rilevanza, grant number 00949-2018). W.J.V.P. acknowledges FAPERGS (grant number ARD#21/2551-0000686-2).
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spelling Quadros, Helenita C.Çapcı, AysunHerrmann, LarsD’Alessandro, SarahFontinha, DianaAzevedo, RaquelVillarreal, WilmerBasilico, NicolettaPrudêncio, MiguelTsogoeva, Svetlana B.Moreira, Diogo R. M.2021-12-09T17:56:27Z2021-12-09T17:56:27Z2021QUADROS, Helenita C. et al. Studies of Potency and Efficacy of an Optimized Artemisinin-Quinoline Hybrid against Multiple Stages of the Plasmodium Life Cycle. Pharmaceuticals, 2021.1424-8247https://www.arca.fiocruz.br/handle/icict/5025610.3390/ph14111129CAPES doctoral scholarship (Finance Code 001, Brazil). S.B.T. acknowledges the Deutsche Forschungsgemeinschaft (DFG) for funding (grant number TS87/17-1; TS87/23-1, Germany) and the Bavarian State Ministry for Science, Research and Art (Germany). D.R.M.M. acknowledges CNPq (grant No. 305732/2019-6, Brazil), FAPESB (grant number APP0088/2016, Brazil), and Fiocruz/Proep (grant number IGM-002-FIO-20-2-25, Brazil). M.P. was supported by grant PTDC-SAU-INF-29550-2017 (FCT, Portugal). S.D. and N.B. were supported by the by Fondazione Cariplo (grant number 2017-0846), the Ministero dell’Istruzione, dell’Università e della Ricerca (grant number PRIN 2015.4JRJPP_004), and the Ministero degli Affari Esteri e della Cooperazione Internazionale (Progetti di grande rilevanza, grant number 00949-2018). W.J.V.P. acknowledges FAPERGS (grant number ARD#21/2551-0000686-2).Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.University of Erlangen-Nürnberg. Center for Molecular Materials Friedrich-Alexander. Organic Chemistry Chair I and Interdisciplinary. Nikolaus Fiebiger-Straße. Erlangen, Germany.University of Erlangen-Nürnberg. Center for Molecular Materials Friedrich-Alexander. Organic Chemistry Chair I and Interdisciplinary. Nikolaus Fiebiger-Straße. Erlangen, Germany.Università degli Studi di Milano. Dipartimento di Scienze Farmacologiche e Biomolecolari. Milan, Italy.Universidade de Lisboa. Faculdade de Medicina. Instituto de Medicina Molecular. Lisboa, Portugal.Universidade de Lisboa. Faculdade de Medicina. Instituto de Medicina Molecular. Lisboa, Portugal.,Universidade Federal do Rio Grande do Sul. Instituto de Química. Grupo de Química Inorgânica Medicinal e Reações Aplicadas. Porto Alegre, RS, Brasil.Universitá degli Studi di Milano. Dipartimento di Scienze Biomediche, Chirurgiche e Odontoiatriche. Milan, Italy.Universidade de Lisboa. Faculdade de Medicina. Instituto de Medicina Molecular. Lisboa, Portugal.University of Erlangen-Nürnberg. Center for Molecular Materials Friedrich-Alexander. Organic Chemistry Chair I and Interdisciplinary. Nikolaus Fiebiger-Straße. Erlangen, Germany.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.A recently developed artemisinin-quinoline hybrid, named 163A, has been shown to display potent activity against the asexual blood stage of Plasmodium, the malaria parasite. In this study, we determined its in vitro cytotoxicity to mammalian cells, its potency to suppress P. berghei hepatic infection and to decrease the viability of P. falciparum gametocytes, in addition to determining whether the drug exhibits efficacy of a P. berghei infection in mice. This hybrid compound has a low level of cytotoxicity to mammalian cells and, conversely, a high level of selectivity. It is potent in the prevention of hepatic stage development as well as in killing gametocytes, denoting a potential blockage of malaria transmission. The hybrid presents a potent inhibitory activity for beta-hematin crystal formation, in which subsequent assays revealed that its endoperoxide component undergoes bioactivation by reductive reaction with ferrous heme towards the formation of heme-drug adducts; in parallel, the 7-chloroquinoline component has binding affinity for ferric hemin. Both structural components of the hybrid co-operate to enhance the inhibition of betahematin, and this bitopic ligand property is essential for arresting the growth of asexual blood parasites. We demonstrated the in vivo efficacy of the hybrid as an erythrocytic schizonticide agent in comparison to a chloroquine/artemisinin combination therapy. Collectively, the findings suggest that the bitopic property of the hybrid is highly operative on heme detoxification suppression, and this provides compelling evidence for explaining the action of the hybrid on the asexual blood stage. For sporozoite and gametocyte stages, the hybrid conserves the potency typically observed for endoperoxide drugs, and this is possibly achieved due to the redox chemistry of endoperoxide components with ferrous heme.engMDPIMaláriaPlasmodiumInfecçõesEsporozoítosHeminaCloroquinaMalariaPlasmodiumHemozoinHeterobivalentArtemisininHybridsStudies of Potency and Efficacy of an Optimized Artemisinin-Quinoline Hybrid against Multiple Stages of the Plasmodium Life Cycleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83097https://www.arca.fiocruz.br/bitstream/icict/50256/1/license.txt36b51ef91c52b5338d9d29ba0cc807bcMD51ORIGINALQuadros, Elenita C. Studies of....pdfQuadros, Elenita C. Studies of....pdfapplication/pdf2909034https://www.arca.fiocruz.br/bitstream/icict/50256/2/Quadros%2c%20Elenita%20C.%20Studies%20of....pdf047132fabbbe210ed8243a78b675de12MD52icict/502562023-03-15 14:34:32.112oai:www.arca.fiocruz.br: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Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-03-15T17:34:32Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv Studies of Potency and Efficacy of an Optimized Artemisinin-Quinoline Hybrid against Multiple Stages of the Plasmodium Life Cycle
title Studies of Potency and Efficacy of an Optimized Artemisinin-Quinoline Hybrid against Multiple Stages of the Plasmodium Life Cycle
spellingShingle Studies of Potency and Efficacy of an Optimized Artemisinin-Quinoline Hybrid against Multiple Stages of the Plasmodium Life Cycle
Quadros, Helenita C.
Malária
Plasmodium
Infecções
Esporozoítos
Hemina
Cloroquina
Malaria
Plasmodium
Hemozoin
Heterobivalent
Artemisinin
Hybrids
title_short Studies of Potency and Efficacy of an Optimized Artemisinin-Quinoline Hybrid against Multiple Stages of the Plasmodium Life Cycle
title_full Studies of Potency and Efficacy of an Optimized Artemisinin-Quinoline Hybrid against Multiple Stages of the Plasmodium Life Cycle
title_fullStr Studies of Potency and Efficacy of an Optimized Artemisinin-Quinoline Hybrid against Multiple Stages of the Plasmodium Life Cycle
title_full_unstemmed Studies of Potency and Efficacy of an Optimized Artemisinin-Quinoline Hybrid against Multiple Stages of the Plasmodium Life Cycle
title_sort Studies of Potency and Efficacy of an Optimized Artemisinin-Quinoline Hybrid against Multiple Stages of the Plasmodium Life Cycle
author Quadros, Helenita C.
author_facet Quadros, Helenita C.
Çapcı, Aysun
Herrmann, Lars
D’Alessandro, Sarah
Fontinha, Diana
Azevedo, Raquel
Villarreal, Wilmer
Basilico, Nicoletta
Prudêncio, Miguel
Tsogoeva, Svetlana B.
Moreira, Diogo R. M.
author_role author
author2 Çapcı, Aysun
Herrmann, Lars
D’Alessandro, Sarah
Fontinha, Diana
Azevedo, Raquel
Villarreal, Wilmer
Basilico, Nicoletta
Prudêncio, Miguel
Tsogoeva, Svetlana B.
Moreira, Diogo R. M.
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Quadros, Helenita C.
Çapcı, Aysun
Herrmann, Lars
D’Alessandro, Sarah
Fontinha, Diana
Azevedo, Raquel
Villarreal, Wilmer
Basilico, Nicoletta
Prudêncio, Miguel
Tsogoeva, Svetlana B.
Moreira, Diogo R. M.
dc.subject.other.pt_BR.fl_str_mv Malária
Plasmodium
Infecções
Esporozoítos
Hemina
Cloroquina
topic Malária
Plasmodium
Infecções
Esporozoítos
Hemina
Cloroquina
Malaria
Plasmodium
Hemozoin
Heterobivalent
Artemisinin
Hybrids
dc.subject.en.pt_BR.fl_str_mv Malaria
Plasmodium
Hemozoin
Heterobivalent
Artemisinin
Hybrids
description CAPES doctoral scholarship (Finance Code 001, Brazil). S.B.T. acknowledges the Deutsche Forschungsgemeinschaft (DFG) for funding (grant number TS87/17-1; TS87/23-1, Germany) and the Bavarian State Ministry for Science, Research and Art (Germany). D.R.M.M. acknowledges CNPq (grant No. 305732/2019-6, Brazil), FAPESB (grant number APP0088/2016, Brazil), and Fiocruz/Proep (grant number IGM-002-FIO-20-2-25, Brazil). M.P. was supported by grant PTDC-SAU-INF-29550-2017 (FCT, Portugal). S.D. and N.B. were supported by the by Fondazione Cariplo (grant number 2017-0846), the Ministero dell’Istruzione, dell’Università e della Ricerca (grant number PRIN 2015.4JRJPP_004), and the Ministero degli Affari Esteri e della Cooperazione Internazionale (Progetti di grande rilevanza, grant number 00949-2018). W.J.V.P. acknowledges FAPERGS (grant number ARD#21/2551-0000686-2).
publishDate 2021
dc.date.accessioned.fl_str_mv 2021-12-09T17:56:27Z
dc.date.available.fl_str_mv 2021-12-09T17:56:27Z
dc.date.issued.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
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status_str publishedVersion
dc.identifier.citation.fl_str_mv QUADROS, Helenita C. et al. Studies of Potency and Efficacy of an Optimized Artemisinin-Quinoline Hybrid against Multiple Stages of the Plasmodium Life Cycle. Pharmaceuticals, 2021.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/50256
dc.identifier.issn.pt_BR.fl_str_mv 1424-8247
dc.identifier.doi.none.fl_str_mv 10.3390/ph14111129
identifier_str_mv QUADROS, Helenita C. et al. Studies of Potency and Efficacy of an Optimized Artemisinin-Quinoline Hybrid against Multiple Stages of the Plasmodium Life Cycle. Pharmaceuticals, 2021.
1424-8247
10.3390/ph14111129
url https://www.arca.fiocruz.br/handle/icict/50256
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
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collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/50256/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/50256/2/Quadros%2c%20Elenita%20C.%20Studies%20of....pdf
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