摘要/Abstract

为了寻找新型高效抗肿瘤候选药物，设计并合成了一系列新型三甲氧基苯基-喹啉杂合体，并评估了目标化合物对三种不同肿瘤细胞EC-109（人食管癌细胞），PC-3（人前列腺癌细胞）和MGC-803（人胃癌细胞）的抗增殖活性.结果表明N-（3-（氯甲基）苄基）-3，4，5-三甲氧基-N-（喹啉-8-基）苯甲酰胺（12j）对PC-3细胞具有良好的抗增殖活性，IC₅₀值为9.23 μmol/L.同时，化合物12j抑制PC-3细胞增殖和克隆形成.进一步机制研究表明，化合物12j可以将PC-3细胞阻滞在G2/M期，并通过激活内源性和外源性凋亡途径诱导细胞凋亡.
关键词: 喹啉, 三甲氧基苯基, 抗肿瘤活性, 细胞周期阻滞, 凋亡
With the expectation to find out novel and effective anti-tumor agents, a series of novel trimethoxyphenyl-quinoline hybrids were designed, synthesized and evaluated for antiproliferative activity against three human cancer cell lines (EC-109, human esophageal cancer cells; PC-3, human prostate cancer cells; MGC-803, human gastric cancer cells). N-(3-(Chloromethyl)benzyl)-3,4,5-trimethoxy-N-(quinolin-8-yl)benzamide (12j) showed the most potent antitumor activity against PC-3 cells with IC₅₀ value of 9.23 μmol/L. Meanwhile, compound 12j inhibited the cell viability and colony formation of PC-3 cells. Further mechanism studies revealed that compound 12j could arrest PC-3 cells in G2/M phase and induce cell apoptosis via activating intrinsic and extrinsic apoptosis pathway.
Key words: quinoline, trimethoxyphenyl, anticancer, cell cycle arrest, apoptosis


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