Brasil | Article

Antimalarial and anti-inflammatory activities of new chloroquine and primaquine hybrids: Targeting the blockade of malaria parasite transmission

dc.creatorBoechat, Nubia
dc.creatorCarvalho, Rita C C
dc.creatorFerreira, Maria de Lourdes G
dc.creatorCoutinho, Julia Penna
dc.creatorSa, Paula M
dc.creatorSeito, Leonardo N
dc.creatorRosas, Elaine C
dc.creatorKrettli, Antoniana Ursine
dc.creatorBastos, Monica M
dc.creatorPinheiro, Luiz C S
dc.date2023-05-24T17:55:57Z
dc.date2023-05-24T17:55:57Z
dc.date2020
dc.date.accessioned2023-09-26T21:09:18Z
dc.date.available2023-09-26T21:09:18Z
dc.identifierBOECHAT, 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.
dc.identifier0968-0896
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/58629
dc.identifier10.1016/j.bmc.2020.115832
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8870017
dc.descriptionMalaria 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.
dc.description2099-12-31
dc.formatapplication/pdf
dc.languageeng
dc.publisherElsevier Science
dc.rightsrestricted access
dc.subjectMalaria
dc.subjectPrimaquine
dc.subjectAnti-inflammatory
dc.subjectAntiplasmodial
dc.titleAntimalarial and anti-inflammatory activities of new chloroquine and primaquine hybrids: Targeting the blockade of malaria parasite transmission
dc.typeArticle


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