雷公藤中的雷公藤內(nèi)酯醇具有抗腫瘤、免疫抑制等多種生物活性，但是副作用大等特點限制了臨床的使用。為了獲得高效低毒的雷公藤內(nèi)酯醇衍生物，對其結(jié)構(gòu)進行了改造。近5年來對雷公藤內(nèi)酯醇的結(jié)構(gòu)改造又有了新進展，包括對其14位羥基、不飽和五元內(nèi)酯環(huán)、B環(huán)、13位異丙基和10位甲基的結(jié)構(gòu)改造，得到一系列衍生物。其中對14位羥基進行前藥設計，從而降低了雷公藤內(nèi)酯醇的毒性，14位羥基改造為α-羥基衍生物后發(fā)現(xiàn)了與雷公藤內(nèi)酯醇活性相當?shù)难苌?。綜述了近5年來對雷公藤內(nèi)酯醇的結(jié)構(gòu)改造及構(gòu)效關(guān)系研究進展。

Triptolide, an ingredient of Tripterygium wilfordii, has been demonstrated to possess many biological activities such as immunosuppressive activity, antitumor activity and so on. However due to its severe toxicity, triptolide limited its clinical use. To obtain derivatives with high efficacy and low toxicity, structural modifications were conducted. A new progress was made on triptolide structural modifications in recent five years, including C-14-hydroxyl group, the lactone ring, B ring, C-13 isopropyl group and C-10 methyl group modified derivatives, and a series of derivatives were obtained. C-14-hydroxyl prodrug design reduced the toxicity of triptolide; An epi-tripolide derivative by introducing of the indazole aminomethyl group showed comparable potency with triptolide. This review will focus on structural modification and structure-activity relationship of triptolide in recent five years.

福建省自然科學基金資助項目（2017J01141）；福建省省屬公益類科研院所基本科研專項（2015R1031-1）