Novel derivatives of puberulic acid were synthesized and their antimalarial properties were evaluated in vitro against the Plasmodium falciparum K1 parasite strain, cytotoxicity against a human diploid embryonic cell line MRC-5, and in vivo efficacy using a Plasmodium berghei-infected mouse model. From previous information that three hydroxy groups on the tropone framework were essential for antimalarial activity, we converted the carboxylic acid moiety into the corresponding esters, amides, and ketones. These derivatives showed antimalarial activity against chloroquine-resistant Plasmodium in vitro equivalent to puberulic acid. We identified that the pentane-3-yl ester, cyclohexyl ester, iso-butyl ketone, cyclohexyl methyl ketone all show an especially potent antiparasitic effect in vivo at an oral dose of 15 mg/kg without any apparent toxicity. These esters were more effective than the existing commonly used antimalarial drug, artesunate.

合成了新的青春痘衍生物，并在体外对恶性疟原虫K1 寄生虫菌株的抗疟特性、对人二倍体胚胎细胞系 MRC-5 的细胞毒性以及使用伯氏疟原虫感染的小鼠模型的体内功效进行了评估。根据之前的信息，托酮骨架上的三个羟基对于抗疟活性至关重要，我们将羧酸部分转化为相应的酯、酰胺和酮。这些衍生物在体外对氯喹抗性疟原虫的抗疟活性与小春藤酸相当。我们确定了戊烷-3-基酯、环己基酯、异丁基酮、环己基甲基酮在 15 mg/kg 的口服剂量下都显示出特别有效的体内抗寄生虫作用，而没有任何明显的毒性。这些酯比现有的常用抗疟药青蒿琥酯更有效。