First synthesis of 3,16,20-polyoxygenated cholestanes, new cytotoxic steroids from the gorgonian Leptogorgia sarmentosa

Using tigogenin as starting material, (20 S )-20-hydroxycholestane-3,6-dione ( 1 ), (16 S , 20 S )-16,20-dihydroxycholestan-3-one ( 2 ), (20 S )-20-hydroxycholest-1-ene-3,16-dione ( 3 ) and (20 S )-20-hydroxycholest-4-ene-3,16-dione ( 4 ), natural polyoxygenated steroids from the gorgonian, Leptogorgia sarmentosa , were synthesized in four steps. Antitumor activity against three tumor cell lines (breast cancer, MCF7, lung cancer NCI and oral cancer KB) was evaluated. Two compounds ( 3 and 4 ) showed strong activity against NCI (IC 50 6.16 and 10.51 μM) and moderate activity against MCF7 and KB, the IC 50 being in the range 30.65–47.22 μM. Compound 2 showed moderate activity against NCI (IC 50 42.68 μM) but was inactive against MCF7 and KB whereas compound 1 showed no activity against all tested cells.