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; R₁ = Cl) was more potent than CQ in vitro, and 8 (n = 4; R₁ = 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 TNFα 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.

疟疾是一种不仅需要抗疟原虫而且还需要减少感染症状（如发烧和发炎）的新药。从氯喹（CQ）和伯氨喹（PQ）设计了一系列21种杂化化合物，这些化合物与苯乙酸抗炎药中存在的药效基团相连。这些化合物被设计为具有双重活性：即，能够杀死疟原虫并且仍然对由疟疾感染引起的炎症过程起作用。用九种不同的生物学方法测定化合物。羰基化的CQ衍生物6（n = 3; R ₁  = Cl）在体外比CQ更有效，而8（n = 4; R ₁ ＝ H）在第7天将伯氏疟原虫寄生虫病降低至37％。羰基化的PQ衍生物17（R ＝ Br）的效力略低于PQ。所述宝石二氟PQ衍生物20（R = Cl）的表现出的蚊子的疟疾孢子生殖周期的高传输封锁。化合物6和20剂量依赖性地减少LPS刺激的J774A.1巨噬细胞产生的一氧化氮（NO）的产生并抑制TNFα的产生。我们的结果表明，在规划用作阻止恶性疟原虫和间日疟原虫引起的疟疾的传播阻断药物的新化学实体方面，可行且有趣的方法 以及与此疾病有关的抗炎过程。