First synthesis of 3,16,20-polyoxygenated cholestanes, new cytotoxic steroids from the gorgonian Leptogorgia sarmentosa.
Using tigogenin as starting material, (20S)-20-hydroxycholestane-3,6-dione (1), (16S, 20S)-16,20-dihydroxycholestan-3-one (2), (20S)-20-hydroxycholest-1-ene-3,16-dione (3) and (20S)-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 microM) and moderate activity against MCF7 and KB, the IC(50) being in the range 30.65-47.22 microM. Compound 2 showed moderate activity against NCI (IC(50) 42.68 microM) but was inactive against MCF7 and KB whereas compound 1 showed no activity against all tested cells.
Boonananwong
Suthinee
S
Natural Products and Organic Synthesis Research Unit (NPOS), Department of Chemistry, Faculty of Science, Kasetsart University, Chatuchak, Bangkok 10900, Thailand.
Kongkathip
Boonsong
B
Kongkathip
Ngampong
N
D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy; D018288:Carcinoma, Small Cell / Q000188:drug therapy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D045744:Cell Line, Tumor; D002776:Cholestanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D003063:Cnidaria / Q000737:chemistry*; D003603:Cytotoxins / Q000737:chemistry* / Q000302:isolation & purification; D004353:Drug Evaluation, Preclinical; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000188:drug therapy; D015394:Molecular Structure; D009062:Mouth Neoplasms / Q000188:drug therapy; D013256:Steroids / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*
D000970:Antineoplastic Agents; D002776:Cholestanes; D003603:Cytotoxins; D013256:Steroids