对叶大戟是传统的新疆维吾尔药材，具有利水消肿，镇咳平喘，燥湿开胃，健脑益智的作用。临床上长期用于治疗腹胀胃弱，食少健忘，语言不利，肢体瘫痪，皮肤疾病等病症。在苏孜阿甫片、复方苏孜阿甫蜜膏、加瓦日西库木尼、依力提提蜜膏、苏孜阿甫软膏、苏扎甫散、赛拉尼散等十几种成熟的维吾尔医复方药中作为主要成分应用。我们前期从对叶大戟中分离得到的假白榄烷型大环二萜类化合物（ES2）具有显著的多药耐药逆转活性，其活性优于阳性对照药维拉帕米。在此基础上，我们对该ES2进行了初步的作用机制研究，初步探讨了该化合物的作用靶点。本课题拟通过对该化合物进行结构修饰，合成一系列的ES2衍生物，并对所合成的衍生物进行细胞毒性、多药耐药逆转活性等生物活性筛选，分析该系列化合物的结构与活性之间的构效关系，以期发现高效的新型先导化合物，并充分揭示其作用机理，为自主知识产权的创新药物开发及当地资源的有效利用提供理论依据。

Euphorbia sororia A. Schrenk, an annual herb, is mainly found in Xinjiang Uyghur Autonomous Region of China and Central Asia. Fructus of E. sororia, a traditional Uyghur medicine, has been used to cure abdominal pain, abdominal distention, skin disease, paralysis and improve intelligence and appetite. Our previous phytochemical investigations on this plant yielded the jatrophane-type macrocyclic diterpenoid, named ES2, which displayed potent multidrug resistance reversal activity. On this basis, a preliminary study have been conducted to explore the MDR reversal mechanism of the compound ES2. And we are intend to synthesis a series of derivatives of ES2 and the jatrophane-type macrocyclic diterpenoids, serving for further biological activity screening, such as cytotoxicity and MDR reversal activity, in order to reveal the structure-activity relationship of these compounds. New effective lead compounds and their pharmacological mechanism are expected to be found, to provide the theoretical basis for the development of innovative property drugs.