Twenty six peroxides belonging to bridged 1,2,4,5‐tetraoxanes, bridged 1,2,4‐trioxolanes (ozonides), and tricyclic monoperoxides were evaluated for their in vitro antimalarial activity against Plasmodium falciparum (3D7) and for their cytotoxic activities against immortalized human normal fibroblast (CCD19Lu), liver (LO₂), and lung (BEAS‐2B) cell lines as well as human liver (HepG2) and lung (A549) cancer‐cell lines. Synthetic ozonides were shown to have the highest cytotoxicity on HepG2 (IC₅₀=0.19–0.59 μm), and some of these compounds selectively targeted liver cancer (selectivity index values for compounds 13 a and 14 a are 20 and 28, respectively) at levels that, in some cases, were higher than those of paclitaxel, artemisinin, and artesunic acid. In contrast some ozonides showed only moderate antimalarial activity against the chloroquine‐sensitive 3D7 strain of P. falciparum (IC₅₀ from 2.76 to 24.2 μm; 12 b, IC₅₀=2.76 μm; 13 a, IC₅₀=20.14 μm; 14 a, IC₅₀=6.32 μm). These results suggest that these derivatives have divergent mechanisms of action against cancer cells and malaria‐infected cells. A cyclic voltammetry study of the peroxides was performed, but most of the compounds did not show direct correlation in oxidative capacity–activity. Our findings offer a new source of antimalarial and anticancer agents through structural modification of peroxide compounds.

中文翻译：

---

新型过氧化物作为有望的抗癌药物，其抗疟药活性异常下降

评估了桥接的1,2,4,5-四恶烷，桥接的1,2,4-三氧戊环（恶臭）和三环一过氧化物中的26种过氧化物对恶性疟原虫（3D7）的体外抗疟活性和细胞毒性活性对抗永生化的人正常成纤维细胞（CCD19Lu），肝（LO ₂）和肺（BEAS-2B）细胞系以及人肝（HepG2）和肺（A549）癌细胞系。合成的臭氧化物显示出具有对HepG2（IC最高的细胞毒性₅₀ = 0.19-0.59μ米），以及一些这些化合物选择性地靶向于化合物肝癌（选择性指数值的13和14一分别为20和28），在某些情况下，其含量高于紫杉醇，青蒿素和青蒿琥酯的水平。相反一些臭氧化物显示出对的氯喹敏感株3D7仅适度抗疟疾活性恶性疟原虫（IC ₅₀从2.76至24.2μ米; 12b中，IC ₅₀ = 2.76μ米; 13，IC ₅₀ = 20.14μ米; 14，IC ₅₀ = 6.32μ米）。这些结果表明，这些衍生物对癌细胞和疟疾感染细胞具有不同的作用机制。进行了对过氧化物的循环伏安法研究，但大多数化合物并未显示出氧化能力与活性之间的直接关系。通过过氧化物化合物的结构修饰，我们的发现为抗疟和抗癌药物提供了新的来源。