Fluorinated vitamin D-3 analog with in vivo anticancer activity

To synthesize vitamin Dg analogs with in vivo anticancer activity but not calcemic activity, eight different fluorinated analogs were synthesized and structure-activity relationships were determined. Modifications such as 26,27-fluorination, side chain homologation and introduction of a hydroxyl group were carried out. The fluorinated vitamin D-3 analog, (22S)-26,26,26,27,27,27-hexafluoro-24-homo-1 alpha,22,25-trihydroxyvitamin D-3, was found to inhibit the growth of human colon cancer cells (HT-29) in culture to an extent ten times that of the active metabolite of vitamin D-3, 1 alpha,25-dihydroxyvitamin D-3. The growth of human colon cancer (HT-29) implanted beneath the renal capsule of SCID (severe combined immunodeficiency) mice was suppressed by 63% by the fluorinated analog (3 mu g/kg body weight i.p. every other day, 5 times) with no increase in serum calcium.