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.

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A structure-activity relationship (SAR) study of bastadin 6 (1), a brominated tyrosine-derived metabolite from Indonesian marine sponge having a potent anti-angiogenic activity, was executed. The syntheses and their biological evaluation of the oxime-modified analogues and bromine-modified analogues revealed that both the oxime moieties and bromine atoms in bastadin 6 (1) play an important role to show the potent and selective anti-proliferative activity against human umbilical vein endothelial cells (HUVECs).