紫杉烷类多药耐药逆转剂的合成及其逆转耐药活性

Synthesis and drug resistant reversal activities of taxane-like multi-drug resistant reversal agents

目的 设计合成一系列新型紫杉烷类化合物并进行逆转多药耐药肿瘤细胞耐药活性的筛选。方法 以本所生物合成的紫杉烷 ,SinenxanA为原料 ,合成了 1 0个 (I1～ 7,II1 ,2 ,III)新的紫杉烷类化合物 ,其结构经FABMS ,2DNMR确证 ,并对多药耐药癌细胞进行了逆转耐药性的试验。结果 9个 (I2～ 7,II1 ,2 ,III)化合物对多药耐药的人口腔上皮癌细胞KB V2 0 0 ,能够显著逆转其耐药性 ,增强抗癌药的活性 ,其中化合物I2 ,I3 ,I4逆转活性明显好于已知对照药Verapamil。结论 紫杉烷类化合物作为多药耐药逆转剂有较好的逆转耐药活性 。

Aim To design and synthesize a series of new taxoids with a 5-O-sidechain, and to test the multi-drug resistant reversal activity of these compound on KB/V200 cells which is 180 times more resistant to vincristine. Methods Using Sinenxan A as a common synthetic starting material, three different types of 5-O-sidechain molecules were synthesized through different route. For type I compounds, 14-acetoxy of Sinenxan A was selectively removed by hydrolysis, xanthation and reduction with tributyltin; A C-10-ox...