本项目拟在没有改变紫杉醇原有构效关系基础上，在紫杉醇原有结构上新增加创新基团,即以抑制p53-MDM2结合为治疗靶点的氧化吲哚骨架拼接到以微管蛋白为治疗靶点的紫杉醇母核上，杂合成多机制抗肿瘤活性紫杉烷类化合物。基于在前期研究基础上，继续对贵州产南方红豆杉针叶中巴卡亭III类似物进行深入提取分离，计划分离8个以上巴卡亭III类似物；通过不对称合成的方法合成含氨基醇酸氧化吲哚骨架,然后再通过半合成方法，拼接到巴卡亭III类似物上合成新型紫杉烷类化合物，计划合成60余个新型紫杉烷类化合物；通过改变所合成的新型紫杉烷类化合物上取代基为水溶性基团，增加其水溶性，期待改善其生物利用度。通过对所合成的新型紫杉烷类化合物进行抗肿瘤活性、多药耐药性、多靶点机制、生物利用度等研究，计划筛选出1种以上高活性新型紫杉烷类化合物. 期待为肿瘤疾病的治疗发现潜在的新靶点，为治疗肿瘤疾病创新药物的设计提供新的思路。

The project intends to synthesize the novel anti-tumor activity multi-mechanism taxanes on the basis of the original taxol structure-activity relationship, through hybridization of alkyd oxindole derivatives of therapeutic target for p53-MDM2 and TAXOL derivatives of therapeutic target for tubulin. Based on preliminary studies, continuous studies on seperation baccatin ІІІ analogs from Guizhou Taxus needles, planning to separate more than eight baccatin III analogs; Asymmetric synthesis of the side chain alkyd oxindole derivatives, through semi-synthesic methods for docking the side chains with baccatin III analogs, planning to synthesis of more than sixty novel TAXOL derivatives; Through modifing the substituents of novel TAXOL derivatives to water-soluble groups, studies on improving water solubility, expecting to solve low bioavailability problems; Trough studies on the novel TAXOL derivatives anti-tumor activities in screemig, multidrug resistance, multi-target mechanism and bioavailability, et al, planning to screeming high activity of one or more new taxanes.The progect will reveal the potential targets in the treatment of cancer, and provide a new idea to the development of anti-cancer medicines.