苄普地尔衍生物的合成及对多药耐药性的逆转作用

Synthesis of Bepridil Derivatives and Reversal Activity of Multidrug Resistance

设计并合成了5个苄普地尔(BEP)的衍生物,并对其逆转多药耐药性作用进行了初步研究。结构均经红外光谱、核磁共振氢谱和质谱确证。药理实验以Fura-2/AM法测定P-糖蛋白功能,结果显示Ⅰa～Ⅰe都具有逆转多药抗药性的活性,其中Ⅰc和Ⅰe的活性与BEP相当,Ⅰb显著高于BEP(P<0.05)。

To explore the reversal of multidrug resistance （MDR） by bepridil, five derivatives were designed and synthesized. The structures were confirmed by IR, 1^HNMR, and MS. The compounds were studied for MDR reversal activity by measuring the function of permeability glycoprotein with Fura-2/AM. The results showed that all five derivatives had MDR reversal activity. Among them, Ⅰc and Ⅰe were comparable to BEP and Ⅰ b was more potent than BEP（P〈0.05）.