Synthesis and biological evaluation of JL-A7 derivatives as potent ABCB1 inhibitors
Synthesis and biological evaluation of JL-A7 derivatives as potent ABCB1 inhibitors
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JL-A7 衍生物作为有效 ABCB1 抑制剂的合成和生物学评价
DOI：
10.1016/j.bmc.2017.06.015
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发表时间：
2017
影响因子：
3.5
通讯作者：
Qian Hai
中科院分区：
文献类型：
--
作者：
Pan Miaobo;Cui Jian;Jiao Lei;Ghaleb Hesham;Liao Chen;Zhou Jiaqi;Kairuki Mutta;Lin Haiyan;Huang Wenlong;Qian Hai
肿瘤化疗失败通常是由于ATP结合盒(ABC)转运体(尤其是ABCB1)的过度表达，导致多种结构和药理无关的药物外流。ABCB1抑制剂可逆转多药耐药(MDR)现象。目前，以三氮唑-N-乙基-四氢异喹啉为骨架的先导化合物JL-A7已设计合成了18个化合物。在Para位置上的替换产生了对ABCB1的高活性。此外，化合物5还能有效阻断ABCB1的药物外排功能，增加抗癌药物在MDR细胞中的蓄积，达到有效的治疗浓度。
Cancer chemotherapy failure is often due to the overexpression of ATP-binding cassette (ABC) transporters (particularly ABCB1), resulting in a variety of structurally and pharmacologically unrelated drugs efflux. The multidrug resistance (MDR) phenomenon could be reversed by ABCB1 inhibitors. Now, JL-A7 as the lead compound based on a triazol-N-ethyl-tetrahydroisoquinoline scaffold, 18 compounds were designed and synthesized. Substitution in para positions yielded high activities toward ABCB1. Moreover, compound5could effectively block the drug efflux function of ABCB1 and increase the accumulation of anti-cancer drugs to achieve effective treatment concentration in MDR cells.