Antimalarial activity and mechanisms of action of two novel 4-aminoquinolines against chloroquine-resistant parasites
| Main Author: | |
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| Publication Date: | 2012 |
| Other Authors: | , , , , , , |
| Format: | Article |
| Language: | eng |
| Source: | Repositório Institucional da FIOCRUZ (ARCA) |
| DOI: | 10.1371/journal.pone.0037259 |
| Download full: | https://arca.fiocruz.br/handle/icict/7321 |
Summary: | Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG Brazil/Universidade Federal de Minas Gerais. Faculdade de Medicina. Programa de Pos Graduação em Medicina Molecular. Belo Horizonte, MG, Brazil |
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Aguiar, Anna Caroline CamposSantos, Raquel de MenesesFigueiredo, Flávio Júnior BarbosaCortopassi, Wilian AugustoPimentel, Andre SilvaFrança, Tanos Celmar CostaMeneghetti, Mario RobertoKrettli, Antoniana Ursine2014-02-18T15:15:58Z2014-02-18T15:15:58Z2012AGUIAR, Anna Caroline Campos et al. Antimalarial activity and mechanisms of action of two novel 4-aminoquinolines against chloroquine-resistant parasites. Plos One. 2012, vol.7, pp. e372591932-6203https://arca.fiocruz.br/handle/icict/732110.1371/journal.pone.0037259engPublic Library Of ScienceAntimalarial activity and mechanisms of action of two novel 4-aminoquinolines against chloroquine-resistant parasitesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG Brazil/Universidade Federal de Minas Gerais. Faculdade de Medicina. Programa de Pos Graduação em Medicina Molecular. Belo Horizonte, MG, BrazilUniversidade Federal do Alagoas. Instituto de Quımica e Biotecnologia. Maceio, Alagoas, BrazilFundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG BrazilInstituto Militar de Engenharia. Laboratorio de Modelagem Molecular Aplicada a Defesa Quımica e Biologica . Rio de Janeiro, RJ, Brazil/ Pontifıcia Universidade Catolica do Rio de Janeiro. Departamento de Quımica. Rio de Janeiro, RJ, BrazilPontifıcia Universidade Catolica do Rio de Janeiro. Departamento de Quımica. Rio de Janeiro, RJ, BrazilInstituto Militar de Engenharia. Laboratorio de Modelagem Molecular Aplicada a Defesa Quımica e Biologica . Rio de Janeiro, RJ, Brazil,Universidade Federal do Alagoas. Instituto de Quımica e Biotecnologia. Maceio, Alagoas, Brazil,Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG Brazil/ Universidade Federal de Minas Gerais. Faculdade de Medicina. Programa de Pos Graduação em Medicina Molecular. Belo Horizonte, MG, BrazilChloroquine (CQ) is a cost effective antimalarial drug with a relatively good safety profile (or therapeutic index). However, CQ is no longer used alone to treat patients with Plasmodium falciparum due to the emergence and spread of CQ-resistant strains, also reported for P. vivax. Despite CQ resistance, novel drug candidates based on the structure of CQ continue to be considered, as in the present work. One CQ analog was synthesized as monoquinoline (MAQ) and compared with a previously synthesized bisquinoline (BAQ), both tested against P. falciparum in vitro and against P. berghei in mice, then evaluated in vitro for their cytotoxicity and ability to inhibit hemozoin formation. Their interactions with residues present in the NADH binding site of P falciparum lactate dehydrogenase were evaluated using docking analysis software. Both compounds were active in the nanomolar range evaluated through the HRPII and hypoxanthine tests. MAQ and BAQ derivatives were not toxic, and both compounds significantly inhibited hemozoin formation, in a dose-dependent manner. MAQ had a higher selectivity index than BAQ and both compounds were weak Pf LDH inhibitors, a result previously reported also for CQ. Taken together, the two CQ analogues represent promising molecules which seem to act in a crucial point for the parasite, inhibiting hemozoin formation.Malariainfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZORIGINALAntimalarial activity and mechanisms of action of two novel 4-aminoquinolines against chloroquine-resistant parasites.pdfAntimalarial activity and mechanisms of action of two novel 4-aminoquinolines against chloroquine-resistant parasites.pdfapplication/pdf2107003https://arca.fiocruz.br/bitstreams/f60d3514-14a4-4961-90ee-810724b5d84b/download42f43fb0f2539233acaaca3606c1b9ecMD51trueAnonymousREADLICENSElicense.txtlicense.txttext/plain; charset=utf-81914https://arca.fiocruz.br/bitstreams/790c665c-75d7-4d64-b868-31a4e718078b/download7d48279ffeed55da8dfe2f8e81f3b81fMD52falseAnonymousREADTEXTAntimalarial activity and mechanisms of action of two novel 4-aminoquinolines against chloroquine-resistant parasites.pdf.txtAntimalarial activity and mechanisms of action of two novel 4-aminoquinolines against chloroquine-resistant parasites.pdf.txtExtracted texttext/plain18https://arca.fiocruz.br/bitstreams/6b643e81-d7c8-41ac-9e88-065d96ee6360/download1bb607118047afc5c385b82385dd931fMD56falseAnonymousREADTHUMBNAILAntimalarial activity and mechanisms of action of two novel 4-aminoquinolines against chloroquine-resistant parasites.pdf.jpgAntimalarial activity and mechanisms of action of two novel 4-aminoquinolines against chloroquine-resistant parasites.pdf.jpgGenerated Thumbnailimage/jpeg5862https://arca.fiocruz.br/bitstreams/de4d3bfc-bc70-4a2f-b5ab-2c77e6bf4d01/download4417318bec8be6e58eab50c5b4a46e1aMD57falseAnonymousREADicict/73212025-07-30 01:46:48.048open.accessoai:arca.fiocruz.br:icict/7321https://arca.fiocruz.brRepositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352025-07-30T04:46:48Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)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 |
| dc.title.none.fl_str_mv |
Antimalarial activity and mechanisms of action of two novel 4-aminoquinolines against chloroquine-resistant parasites |
| title |
Antimalarial activity and mechanisms of action of two novel 4-aminoquinolines against chloroquine-resistant parasites |
| spellingShingle |
Antimalarial activity and mechanisms of action of two novel 4-aminoquinolines against chloroquine-resistant parasites Aguiar, Anna Caroline Campos Malaria |
| title_short |
Antimalarial activity and mechanisms of action of two novel 4-aminoquinolines against chloroquine-resistant parasites |
| title_full |
Antimalarial activity and mechanisms of action of two novel 4-aminoquinolines against chloroquine-resistant parasites |
| title_fullStr |
Antimalarial activity and mechanisms of action of two novel 4-aminoquinolines against chloroquine-resistant parasites |
| title_full_unstemmed |
Antimalarial activity and mechanisms of action of two novel 4-aminoquinolines against chloroquine-resistant parasites |
| title_sort |
Antimalarial activity and mechanisms of action of two novel 4-aminoquinolines against chloroquine-resistant parasites |
| author |
Aguiar, Anna Caroline Campos |
| author_facet |
Aguiar, Anna Caroline Campos Santos, Raquel de Meneses Figueiredo, Flávio Júnior Barbosa Cortopassi, Wilian Augusto Pimentel, Andre Silva França, Tanos Celmar Costa Meneghetti, Mario Roberto Krettli, Antoniana Ursine |
| author_role |
author |
| author2 |
Santos, Raquel de Meneses Figueiredo, Flávio Júnior Barbosa Cortopassi, Wilian Augusto Pimentel, Andre Silva França, Tanos Celmar Costa Meneghetti, Mario Roberto Krettli, Antoniana Ursine |
| author2_role |
author author author author author author author |
| dc.contributor.author.fl_str_mv |
Aguiar, Anna Caroline Campos Santos, Raquel de Meneses Figueiredo, Flávio Júnior Barbosa Cortopassi, Wilian Augusto Pimentel, Andre Silva França, Tanos Celmar Costa Meneghetti, Mario Roberto Krettli, Antoniana Ursine |
| dc.subject.en.none.fl_str_mv |
Malaria |
| topic |
Malaria |
| description |
Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG Brazil/Universidade Federal de Minas Gerais. Faculdade de Medicina. Programa de Pos Graduação em Medicina Molecular. Belo Horizonte, MG, Brazil |
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2012 |
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2012 |
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2014-02-18T15:15:58Z |
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2014-02-18T15:15:58Z |
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AGUIAR, Anna Caroline Campos et al. Antimalarial activity and mechanisms of action of two novel 4-aminoquinolines against chloroquine-resistant parasites. Plos One. 2012, vol.7, pp. e37259 |
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https://arca.fiocruz.br/handle/icict/7321 |
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1932-6203 |
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10.1371/journal.pone.0037259 |
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AGUIAR, Anna Caroline Campos et al. Antimalarial activity and mechanisms of action of two novel 4-aminoquinolines against chloroquine-resistant parasites. Plos One. 2012, vol.7, pp. e37259 1932-6203 10.1371/journal.pone.0037259 |
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