从海洋海绵简单皮质海绵中提取的抗血管生成甾体生物碱皮质抑素A、B、C和D。

Cortistatins A, B, C, and D, anti-angiogenic steroidal alkaloids, from the marine sponge Corticium simplex.

作者信息

Aoki Shunji, Watanabe Yasuo, Sanagawa Mami, Setiawan Andi, Kotoku Naoyuki, Kobayashi Motomasa

机构信息

Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0871, Japan.

出版信息

J Am Chem Soc. 2006 Mar 15;128(10):3148-9. doi: 10.1021/ja057404h.

DOI:10.1021/ja057404h

PMID:16522087

Abstract

Four novel steroidal alkaloids named cortistatins A (1), B (2), C (3), and D (4) consisting of a 9(10-19)-abeo-androstane and isoquinoline skeleton have been isolated from the marine sponge Corticium simplex. The absolute stereostructures of 1-4 were elucidated by detailed 2D NMR, CD, and X-ray crystallographic analyses. Cortistatins A-D inhibited proliferation of human umbilical vein endothelial cells (HUVECs) with high selectivity. Among the four substances, cortistatin A (1) showed the strongest anti-proliferative activity (IC50 = 0.0018 muM) against HUVECs, in which the selective index was more than 3000-fold in comparison with that of normal fibroblast or several tumor cell lines.

摘要

从海洋海绵简单皮质海绵（Corticium simplex）中分离出了四种新型甾体生物碱，分别命名为皮质抑素A（1）、B（2）、C（3）和D（4），它们由一个9(10 - 19)-去甲-雄甾烷和异喹啉骨架组成。通过详细的二维核磁共振（2D NMR）、圆二色光谱（CD）和X射线晶体学分析确定了1 - 4的绝对立体结构。皮质抑素A - D对人脐静脉内皮细胞（HUVECs）的增殖具有高度选择性抑制作用。在这四种物质中，皮质抑素A（1）对HUVECs表现出最强的抗增殖活性（IC50 = 0.0018 μM），与正常成纤维细胞或几种肿瘤细胞系相比，其选择性指数超过3000倍。