Reversal of P-glycoprotein associated multidrug resistance by new isoprenoid derivatives.
Reversal of P-glycoprotein associated multidrug resistance by new isoprenoid derivatives.
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新类异戊二烯衍生物逆转 P-糖蛋白相关的多药耐药性。
DOI：
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发表时间：
2001
期刊：
影响因子：
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通讯作者：
Kanki Komiyama
中科院分区：
文献类型：
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作者：
Masahiko Hayashi;Koji Koike;Mun;M. Kuwano;Takao Kishiye;Kanki Komiyama
为了寻找克服P-糖蛋白相关多药耐药的药物，我们合成了43个新的类异戊二烯衍生物。10种化合物在体外试验中对人MDR型耐药癌KB/VJ-300和MRP型KB/VP-4细胞系有效。N-5228 [反式-N，N '-双（3，4-二甲氧基苄基）-N-茄呢基-1，2-二氨基环己烷，mol. wt1100.481在携带P388/VCR的小鼠中进行测试。它对MDR型耐药肿瘤细胞具有抗肿瘤作用。此外，N-5228增强了[3 H]长春新碱在耐药细胞中的蓄积，并阻断了MDR型耐药细胞膜中P-糖蛋白分子的[3 H]叠氮平光亲和标记。我们认为，N-5228是有前途的作为一个先导化合物在筛选耐药逆转药物的多药耐药癌症。
To find a drug to overcome P-glycoprotein associated multidrug resistance, we synthesized 43 new isoprenoid derivatives. Ten compounds were effective in an in vitro assay with the human MDR-type resistant carcinoma KB/VJ-300 and MRP-type KB/VP-4 cell lines. One of the most effective compounds, N-5228 [trans-N,N'-bis(3,4-dimethoxybenzyl)-N-solanesyl-1,2-diaminocyclohexane, mol. wt 1100.481, was tested in P388/VCR-bearing mice. It showed a antitumor effect on MDR-type resistant tumor cells. Moreover, N-5228 potentiated the accumulation of [3H]vincristine in drug-resistant cells and blocked [3H]azidopine photoaffinity labeling of P-glycoprotein molecules in MDR-type resistant cell membranes. We think that N-5228 is promising as a lead compound in the screening of resistance reversing drugs for multidrug resistant cancers.