Key Laboratory of Drug Targeting and Drug Delivery Systems of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu, China.
Med Chem. 2012 Jul;8(4):742-8. doi: 10.2174/157340612801216148.
Fifteen derivatives of 8-oxocoptisine were prepared based on that 8-oxocoptisine showed potent reversing effect against human cancer cells charactering multidrug resistance (MDR). The derivatives were evaluated for their growth inhibition and effects on reversing P-gp-mediated MDR against MCF-7/AMD cells. 12, 13-dinitro-8-oxocoptisine (6c), the most potential candidate with weak growth inhibition, significantly increased the sensitivity of adriamycin (ADM) against MCF-7/ADM cells by 213-fold at 10 μM that was comparable to the reference compound verapamil. The preliminary structure-activity relationships (SARs) of these derivatives were discussed on the basis of the in vitro MDR reversal activities.
基于 8-氧代苦参碱对具有多药耐药性 (MDR) 特征的人癌细胞具有强大的逆转作用，我们制备了 8-氧代苦参碱的 15 种衍生物。这些衍生物的生长抑制作用及其对逆转 MCF-7/AMD 细胞 P-糖蛋白 (P-gp) 介导的 MDR 的影响进行了评估。具有弱生长抑制作用的 12,13-二硝基-8-氧代苦参碱 (6c) 是最有潜力的候选化合物，在 10 μM 时可使阿霉素 (ADM) 对 MCF-7/ADM 细胞的敏感性增加 213 倍，与参比化合物维拉帕米相当。基于体外 MDR 逆转活性，讨论了这些衍生物的初步构效关系 (SAR)。
