Kotoku Naoyuki, Sumii Yuji, Hayashi Takeshi, Tamura Satoru, Kawachi Takashi, Shiomura Sho, Arai Masayoshi, Kobayashi Motomasa
Graduate School of Pharmaceutical Sciences, Osaka University , 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
ACS Med Chem Lett. 2012 Jul 10;3(8):673-7. doi: 10.1021/ml300143d. eCollection 2012 Aug 9.
Syntheses of structurally simplified analogues of cortistatin A (1), a novel antiangiogenic steroidal alkaloid from Indonesian marine sponge, and their biological activities were investigated. The analogues were designed by considering the 3-D structure of 1. Compound 30, in which the isoquinoline moiety was appended to the planar tetracyclic core structure, showed potent antiproliferative activity against human umbilical vein endothelial cells (HUVECs) together with high selectivity and also showed in vivo antiangiogenic activity and significant antitumor effect by oral administration.
对来自印度尼西亚海洋海绵的新型抗血管生成甾体生物碱皮质抑素A（1）的结构简化类似物进行了合成及其生物活性研究。通过考虑1的三维结构设计了这些类似物。化合物30，其中异喹啉部分连接到平面四环核心结构上，对人脐静脉内皮细胞（HUVEC）显示出强大的抗增殖活性，同时具有高选择性，并且通过口服给药还显示出体内抗血管生成活性和显著的抗肿瘤作用。
