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Six new ( 1 ,  2 ,  6 ,  8 ,  13,  and  20 ) and twenty previously isolated ( 3 – 5 ,  7 ,  9 – 12 ,  14 – 19 , and  21 – 26 ) steroids featuring thirteen different carbocycle motifs were isolated from the organic extract of the soft coral  Sinularia polydactyla  collected from the Hurghada reef in the Red Sea. The structures and the relative configurations of the isolated natural products have been determined based on extensive analysis of their NMR and MS data. The cytotoxic, anti-inflammatory, anti-angiogenic, and neuroprotective activity of compounds  3 – 7 ,  9 – 12 ,  14 – 20 , and  22 – 26 , as well as their effect on androgen receptor-regulated transcription was evaluated in vitro in human tumor and non-cancerous cells. Steroids  22  and  23  showed significant cytotoxicity in the low micromolar range against the HeLa and MCF7 cancer cell lines, while migration of endothelial cells was inhibited by compounds  11 ,  12 ,  22,  and  23  at 20 µM. The results of the androgen receptor (AR) reporter assay showed that compound  11  exhibited the strongest inhibition of AR at 10 µM, while it is noteworthy that steroids  10 ,  16,  and  20  displayed increased inhibition of AR with decreasing concentrations. Additionally, compounds  11  and  23  showed neuroprotective activity on neuron-like SH-SY5Y cells.

Bioactive Steroids from the Red Sea Soft Coral Sinularia polydactyla