化合物结构与代谢激活的毒性分析

The induced toxicity of chemical structure and metabolism activation

药物开发的不同阶段,人们通过系列的体外试验研究、动物实验以及随后人体应用的结果试图揭示药物的毒副作用,目的是为确保人体用药的安全性。其中代谢转化诱导的毒性占据药物毒性的很大一方面,尤其反应性代谢产物引发的毒性近几年越来越引起重视。本文综述了几类代表性化合物结构产生反应性代谢产物的情况,包括苯醌亚胺、噻吩环、氮翁离子、环氧化物、硫脲等,试图从代谢角度揭示药物分子结构与药物毒性之间的关系,为药物的设计与开发提供参考。

A complex series of in vitro tests, animal test and then human exposure can at any stages reveal adverse findings that can be termed toxicity. Metabolism - induced toxicity play an important role in drug toxicity, especially toxicity evoked by reactive metabolites has aroused highly consideration in recent years. The reactive metabolites can covalently modify proteins which are considered as an initial step that may lead to drug - induced organ toxicities. So, description of reactive metabolites of several classical structural drugs was reviewed here, including quinone imines, thiophene rings, nitrenium ions,thioureas, epoxides and et al. It aimed at revealing the relationship between reactive metabolite and drug structure in the view of metabolism,and providing information for drug design and development.