Author | Boechat, Nubia | |
Author | Carvalho, Rita C C | |
Author | Ferreira, Maria de Lourdes G | |
Author | Coutinho, Julia Penna | |
Author | Sa, Paula M | |
Author | Seito, Leonardo N | |
Author | Rosas, Elaine C | |
Author | Krettli, Antoniana Ursine | |
Author | Bastos, Monica M | |
Author | Pinheiro, Luiz C S | |
Access date | 2023-05-24T17:55:57Z | |
Available date | 2023-05-24T17:55:57Z | |
Document date | 2020 | |
Citation | BOECHAT, Nubia. Antimalarial and anti-inflammatory activities of new chloroquine and primaquine hybrids: Targeting the blockade of malaria parasite transmission Bioorg Med Chem., v. 28, n. 24, 115832, 2020. doi: 10.1016/j.bmc.2020.115832. | en_US |
ISSN | 0968-0896 | en_US |
URI | https://www.arca.fiocruz.br/handle/icict/58629 | |
Language | eng | en_US |
Publisher | Elsevier Science | en_US |
Rights | restricted access | en_US |
Title | Antimalarial and anti-inflammatory activities of new chloroquine and primaquine hybrids: Targeting the blockade of malaria parasite transmission | en_US |
Type | Article | en_US |
DOI | 10.1016/j.bmc.2020.115832 | |
Abstract | Malaria is a disease that requires new drugs not only to fight Plasmodium but also to reduce symptoms of infection such as fever and inflammation. A series of 21 hybrid compounds were designed from chloroquine (CQ) and primaquine (PQ) linked to the pharmacophoric group present in phenylacetic anti-inflammatory drugs. These compounds were designed to have dual activity: namely, to be capable of killing Plasmodium and still act on the inflammatory process caused by malaria infection. The compounds were assayed with nine different biological methods. The carbonylated CQ derivative 6 (n = 3; R-1 = Cl) was more potent than CQ in vitro, and 8 (n = 4; R-1 = H) reduced P. berghei parasitemia up to 37% on day 7. The carbonylated PQ derivative 17 (R = Br) was slightly less potent than PQ. The gem-difluoro PQ derivative 20 (R = Cl) exhibited high transmission blockade of the malaria sporogonic cycle in mosquitoes. Compounds 6 and 20 dose-dependently reduced nitric oxide (NO) production and inhibited TNF alpha production by LPS-stimulated J774A.1 macrophages. Our results indicate a viable and interesting approach in planning new chemical entities that act as transmission-blocking drugs for treating malaria caused by P. falciparum and P. vivax and the anti-inflammatory process related to this disease. | en_US |
Affilliation | Fundacao Oswaldo Cruz. Instituto de Tecnologia em Farmacos. Laboratorio de Sintese de Farmacos. Rio de Janeiro, RJ, Brasil | en_US |
Affilliation | Fundacao Oswaldo Cruz. Instituto de Tecnologia em Farmacos. Laboratorio de Sintese de Farmacos. Rio de Janeiro, RJ, Brasil | en_US |
Affilliation | Fundacao Oswaldo Cruz. Instituto de Tecnologia em Farmacos. Laboratorio de Sintese de Farmacos. Rio de Janeiro, RJ, Brasil | en_US |
Affilliation | Fundacao Oswaldo Cruz. Instituto Rene Rachou. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Fundacao Oswaldo Cruz. Instituto de Tecnologia em Farmacos. Laboratorio de Sintese de Farmacos. Rio de Janeiro, RJ, Brasil | en_US |
Affilliation | Fundacao Oswaldo Cruz. Instituto de Tecnologia em Farmacos. Departamento de Farmacologia. Rio de Janeiro, RJ, Brasil. | en_US |
Affilliation | Fundacao Oswaldo Cruz. Instituto de Tecnologia em Farmacos. Departamento de Farmacologia. Rio de Janeiro, RJ, Brasil. | en_US |
Affilliation | Fundacao Oswaldo Cruz. Instituto Rene Rachou. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Fundacao Oswaldo Cruz. Instituto de Tecnologia em Farmacos. Laboratorio de Sintese de Farmacos. Rio de Janeiro, RJ, Brasil | en_US |
Affilliation | Fundacao Oswaldo Cruz. Instituto de Tecnologia em Farmacos. Laboratorio de Sintese de Farmacos. Rio de Janeiro, RJ, Brasil | en_US |
Subject | Malaria | en_US |
Subject | Primaquine | en_US |
Subject | Anti-inflammatory | en_US |
Subject | Antiplasmodial | en_US |
Embargo date | 2099-12-31 | |