School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, P. R. China.
Chem Biodivers. 2012 Jun;9(6):1084-94. doi: 10.1002/cbdv.201100195.
Homocamptothecin (hCPT) is a camptothecin (CPT) derivative with a seven-membered β-hydroxylactone E ring, which shows higher lactone stability and improves topoisomerase I (Topo I) inhibition activity. In an attempt to improve the antitumor activity of homocamptothecins, a series of 7-alkenyl-homocamptothecin derivatives was designed and synthesized based on a semisynthetic route starting from CPT. Most of the synthesized compounds exhibit higher cytotoxic activities on the A-549 tumor cell line than topotecan (TPT). Some compounds such as 2a and 2o show a broad in vitro antitumor spectrum and exhibit superior Topo I-inhibition activity.
羟喜树碱（hCPT）是喜树碱（CPT）的衍生物，具有一个七元β-羟基内酯 E 环，表现出更高的内酯稳定性，并提高拓扑异构酶 I（Topo I）抑制活性。为了提高羟喜树碱的抗肿瘤活性，基于从 CPT 开始的半合成路线，设计并合成了一系列 7-烯基-羟喜树碱衍生物。大多数合成化合物对 A-549 肿瘤细胞系的细胞毒性活性均高于拓扑替康（TPT）。一些化合物，如 2a 和 2o，具有广泛的体外抗肿瘤谱，并表现出优异的 Topo I 抑制活性。
