| Author | Silva, Renata M. R. J. da | |
| Author | Gandi, Marilia O. | |
| Author | Mendonça, Jorge S. | |
| Author | Carvalho, Alcione S. | |
| Author | Coutinho, Julia Penna | |
| Author | Aguiar, Anna Caroline Campos | |
| Author | Krettli, Antoniana Ursine | |
| Author | Boechat, Nubia | |
| Access date | 2019-10-10T17:33:55Z | |
| Available date | 2019-10-10T17:33:55Z | |
| Document date | 2019 | |
| Citation | SILVA, Renata M. R. J. da et al. New hybrid trifluoromethylquinolines as antiplasmodium agents. Bioorganic and Medicinal Chemistry, v. 27, n. 6, p. 1002-1008, 2019. | pt_BR |
| ISSN | 0968-0896 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/36357 | |
| Language | eng | pt_BR |
| Publisher | Elsevier Ltd | pt_BR |
| Rights | restricted access | pt_BR |
| Title | New hybrid trifluoromethylquinolines as antiplasmodium agents | pt_BR |
| Type | Article | |
| DOI | 10.1016/j.bmc.2019.01.044 | |
| Abstract | Malaria remains a major public health problem worldwide, and it is responsible for high rates of morbidity and mortality. Resistance to current antimalarial drugs has been identified, and new drugs are urgently needed. In this study, we designed and synthesized seventeen novel quinolines based on the structures of mefloquine ((2,8-bis(trifluoromethyl)quinolin-4-yl)(piperidin-2-yl)methanol) and amodiaquine (4-((7-chloroquinolin-4-yl)amino)-2-((diethylamino)methyl)phenol) using ring bioisosteric replacement and molecular hybridization of the functional groups. The compounds were evaluated in vitro against Plasmodium falciparum and in vivo in mice infected with P. berghei. All derivatives presented anti-P. falciparum activity with IC50 values ranging from 0.083 to 33.0 µM. The compound with the best anti-P. falciparum activity was N-(5-methyl-4H-1,2,4-triazol-3-yl)-2,8-bis(trifluoromethyl)quinolin-4-amine (12) which showed an IC50 of 0.083 µM. The three most active compounds were selected for antimalarial activity tests against P. berghei-infected mice. Compound 12 was the most active on the 5th day after infection, reducing parasitemia by 66%, which is consistent with its in vitro activity. This is an important result as 12, a simpler molecule than mefloquine, does not contain the stereogenic center, and consequently, its synthesis in the laboratory is easier and less expensive. This system proved promising for the design of potential antimalarial compounds. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Programa de Pós-Graduação Farmacologia e Química Medicinal. Instituto de Ciências Biomédicas. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Departamento de Síntese Orgânica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Programa de Pós-Graduação Farmacologia e Química Medicinal. Instituto de Ciências Biomédicas. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Departamento de Síntese Orgânica. Rio de Janeiro, RJ, Brasil / Faculdade de Farmácia Universidade Iguaçu. Nova Iguaçu, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Departamento de Síntese Orgânica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Departamento de Síntese Orgânica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Malária. Belo Horizonte, MG, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Malária. Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Malária. Belo Horizonte, MG, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Departamento de Síntese Orgânica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Amodiaquine | pt_BR |
| Subject | Hybrids | pt_BR |
| Subject | Malaria | pt_BR |
| Subject | Mefloquine | pt_BR |
| Subject | P. falciparum | pt_BR |
| Subject | Quinoline | pt_BR |
| Embargo date | 2035-01-01 | |
