长春碱C-28＇位点的结构改造及其抗肿瘤活性研究

Structure Modification of Vinblastine at C-28' and Its Antitumor Activity

探讨长春碱在C-28'位点的结构修饰,并研究衍生物的抗肿瘤活性.在长春碱的C-28'位使用钯催化偶联的方法合成衍生物,所得化合物经~1H NMR和HRMS-ESI进行了结构表征.进一步以长春碱为对照组,并将其用MTT法在MCF7细胞进行抗肿瘤活性的研究.本试验共6个新颖的长春碱类似物,其中化合物10的活性优于对照品长春碱,两者的IC_(50)分别为0.22μmol/L和0.43μmol/L.

The structure of vinblastine is modified in the C-28＇ site,and the anti-proliferation activity of its analogues are detected. The vinblastine analogues are synthesized by palladium catalyzed-coupling method at C-28＇,and the chemical structures are confirmed by^1 H NMR and HRMS-ESI. Subsequently,the MTT assay is conducted to explore the anti-proliferation activity using MCF7 cancer cells. Six novel vinblastine analogues are obtained,in which the cytotoxic activity of compound 10 is better than that of vinblastine with the IC_（50） values 0. 22 μmol/L and0. 43 μmol/L,respectively.