School of Pharmacy, Second Military Medical University, Shanghai, P. R. China.
Arch Pharm (Weinheim). 2011 Nov;344(11):726-34. doi: 10.1002/ardp.201000402. Epub 2011 Sep 29.
Homocamptothecin (hCPT) is a camptothecin (CPT) homologue with the insertion of a methylene (CH₂) spacer between the alcohol moiety and carbonyl group of the classical six-membered α-hydroxylactone ring. This modification provides higher lactone stability and did not impair its activity against topoisomerase I (Topo I), but rather appears to improve it compared to CPT. In an attempt to improve the antitumor activity of homocamptothecins, a series of novel hCPT derivatives conjugating with dihydropyrimidine (DHPM) derivatives was designed and synthesized based on a synthetic route which couples 7-formylhomocamptothecin with different dihydropyrimidine derivates. Most of the synthesized compounds exhibited good antiproliferative activity on tumor cell lines A549, MDA-MB-435 and HCT116. Furthermore, this class of compounds showed superior Topo I inhibition activity comparable to or higher than CPT.
羟喜树碱（hCPT）是喜树碱（CPT）的同系物，在经典六元α-羟基内脂环的醇部分和羰基之间插入了一个亚甲基（CH₂）间隔基。这种修饰提供了更高的内脂稳定性，并没有损害其对拓扑异构酶 I（Topo I）的活性，反而似乎比 CPT 更能提高其活性。为了提高羟喜树碱的抗肿瘤活性，根据一种将 7-甲酰基羟喜树碱与不同的二氢嘧啶衍生物偶联的合成路线，设计并合成了一系列新型的 hCPT 衍生物与二氢嘧啶衍生物的缀合物。大多数合成的化合物对肿瘤细胞系 A549、MDA-MB-435 和 HCT116 表现出良好的增殖抑制活性。此外，这类化合物显示出与 CPT 相当或更高的优异拓扑异构酶 I 抑制活性。
