Cortistatins A, B, C, and D, anti-angiogenic steroidal alkaloids, from the marine sponge Corticium simplex.
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.
Aoki
Shunji
S
Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0871, Japan.
Watanabe
Yasuo
Y
Sanagawa
Mami
M
Setiawan
Andi
A
Kotoku
Naoyuki
N
Kobayashi
Motomasa
M
D000470:Alkaloids / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D000731:Androstanes / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D020533:Angiogenesis Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D048708:Cell Growth Processes / Q000187:drug effects; D018360:Crystallography, X-Ray; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011161:Porifera / Q000737:chemistry / Q000378:metabolism
D000470:Alkaloids; D000731:Androstanes; D020533:Angiogenesis Inhibitors