Arsenicals have been widely used in the treatment of cancers such as leukemia and other tumors. However, their side effects limit their clinical application. Stiripentol, a second-line adjunctive treatment for epilepsy with a good safety profile, inhibits microsomal cytochrome-P450-family enzymes to extend the retention time of co-administration. Inspired by the metabolism of stiripentol, the 1,3-benzodioxole responsible for the inhibition and its metabolic derivatives were conjugated with arsenical precursors. The fabricated arsenicals were eliminated much slower in mice and maintained an efficient concentration in the blood for a longer time than that of the arsenical precursors. They also performed better in anti-proliferation by inhibiting the thioredoxin system to induce oxidative stress, and concomitantly to initiate apoptosis in vitro and in vivo. The fabricated arsenicals reversed the hemogram of tumor-bearing mice to normal and eliminated the tumor without causing damage to any organs, exhibiting a good design strategy and pre-clinical application for leukemia and other tumors.

中文翻译：

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1,3-苯并二氧戊环衍生物提高砷类药物的抗肿瘤效率

砷已被广泛用于治疗癌症，如白血病和其他肿瘤。然而，它们的副作用限制了它们的临床应用。司替戊醇是一种具有良好安全性的癫痫二线辅助治疗药物，可抑制微粒体细胞色素 P450 家族酶以延长联合给药的保留时间。受司替戊醇代谢的启发，负责抑制的 1,3-苯并二氧戊环及其代谢衍生物与砷前体结合。与砷前体相比，制造的砷在小鼠体内的消除速度要慢得多，并且在血液中保持有效浓度的时间更长。它们还通过抑制硫氧还蛋白系统诱导氧化应激，在抗增殖方面表现更好，并同时在体外和体内启动细胞凋亡。制造的砷剂使荷瘤小鼠的血象图恢复正常并消除了肿瘤，而不会对任何器官造成损害，表现出良好的设计策略和白血病和其他肿瘤的临床前应用。