School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
Eur J Med Chem. 2010 Jun;45(6):2223-8. doi: 10.1016/j.ejmech.2010.01.063. Epub 2010 Feb 1.
A series of novel 9-benzylideneamino derivatives of homocamptothecin were synthesized via Friedlaender cyclization from our obtained intermediate 5. All the compounds were evaluated for in vitro cytotoxicity against three cancer cell lines (A549, LOVO and MDA-MB-435). Most of these derivatives possessed potent growth inhibitory effect on all the tested cell lines and four compounds (6d, 6f, 6i, 6k) showed higher inhibitory activities with the IC50 values of 2.3 nM-9.8 nM against breast cancer cell than topotecan. As compared to CPT, compound 6f revealed higher topoisomerase I inhibitory activity.
我们通过 Friedlaender 环化反应，从获得的中间体 5 合成了一系列新型的 9-苯亚甲基氨基喜树碱衍生物。所有化合物均对三种癌细胞系（A549、LOVO 和 MDA-MB-435）进行了体外细胞毒性评估。这些衍生物大多数对所有测试的细胞系均具有很强的生长抑制作用，其中四个化合物（6d、6f、6i、6k）对乳腺癌细胞的抑制活性更高，IC50 值为 2.3 nM-9.8 nM，优于拓扑替康。与 CPT 相比，化合物 6f 显示出更高的拓扑异构酶 I 抑制活性。
