A series of amide tethered 4-aminoquinoline-naphthalimide hybrids has been synthesized to assess their in vitro antiplasmodial potential against chloroquine-susceptible (3D7) and chloroquine-resistant (W2) strains of Plasmodium falciparum. The most active and noncytotoxic compound had an IC₅₀ value of 0.07 μM against W2 strain and was more active than standard antimalarial drugs, including chloroquine, desethylamodiaquine, and quinine, particularly for drug resistant malaria. The promising scaffold, when subjected to heme binding and molecular modeling studies, was identified as a possible potent inhibitor of hemozoin formation and P. falciparum chloroquine resistance transporter (PfCRT), respectively, and, therefore, could act as a dual function antiplasmodial.

中文翻译：

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酰胺系 4-氨基喹啉-萘二甲酰亚胺杂化物：一类新的可能的双功能抗疟原虫

已经合成了一系列酰胺系 4-氨基喹啉-萘二甲酰亚胺杂化物，以评估它们对恶性疟原虫的氯喹敏感 (3D7) 和氯喹抗性 (W2) 菌株的体外抗疟原虫潜力。活性最强且无细胞毒性的化合物对 W2 菌株的 IC ₅₀值为 0.07 μM，比标准抗疟药物（包括氯喹、去乙基胺二喹啉和奎宁）的活性更高，尤其是对耐药性疟疾。当进行血红素结合和分子建模研究时，这种有前途的支架被确定为可能是血红素形成和恶性疟原虫的有效抑制剂 氯喹抗性转运蛋白 (PfCRT)，因此，可作为双重功能的抗疟原虫。