Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, PR China.
Bioorg Med Chem Lett. 2012 Aug 1;22(15):5008-12. doi: 10.1016/j.bmcl.2012.06.014. Epub 2012 Jun 15.
Twenty scopoletin derivatives were developed by a systematic combinatorial chemical approach and their chemical structures were confirmed by MS, IR, (1)H NMR spectra and elemental analysis. Primary screening against mammary (MCF-7 and MDA-MB 231) and colon (HT-29) carcinoma cells indicated that five compounds (8d, 8g, 8j, 11b and 11g) displayed high antitumor potencies with IC(50) values below 20 μM whereas scopoletin showed IC(50) values above 100 μM. Moreover, the most promising compound 11g was more active than 5-fluorouracil. These results clearly indicated that the modification of the scopoletin structure could greatly increase its antitumor activity in vitro.
通过系统的组合化学方法开发了 20 种东莨菪内酯衍生物，并通过 MS、IR、（1）H NMR 谱和元素分析确证了它们的化学结构。对乳腺癌（MCF-7 和 MDA-MB 231）和结肠癌（HT-29）细胞的初步筛选表明，有 5 种化合物（8d、8g、8j、11b 和 11g）表现出高的抗肿瘤活性，IC50 值低于 20 μM，而东莨菪内酯的 IC50 值高于 100 μM。此外，最有前途的化合物 11g 比 5-氟尿嘧啶更有效。这些结果清楚地表明，东莨菪内酯结构的修饰可以大大提高其体外抗肿瘤活性。
