Takayama Hiroaki

Biological activities of 24-fluoro-1α,25-dihydroxyvitamin D-2 and its 24-epimer

Abstract Biological activities of two epimeric 24-fluorinated vitamin D-2 analogs, 24-fluoro-1α,25-dihydroxyvitamin D-2 [24-F-1,25-(OH) 2 D 2 ] and its 24-epimer [24-epi-24-F-1,25-(OH) 2 D 2 ], were studied and compared with 1α,25-dihydroxyvitamin D-3 [1,25-(OH) 2 D 3 ] and 1α,25-dihydroxyvitamin D-2 [1,25-(OH) 2 D 2 ]. 24-F-1,25-(OH) 2 D 2 was nearly as active as 1,25-(OH) 2 D 3 and 1,25-(OH) 2 D 2 both in regulating calcium metabolism in vivo including bone mineral mobilization and intestinal calcium transport and in inducing differentiation of HL-60 cells. While 24-epi-24-F-1,25-(OH) 2 D 2 showed distinct properties in these two types of the actions. Though the 24-epimer was nearly as potent as 1,25-(OH) 2 D 3 in inducing differentiation of HL-60 cells, it showed little activity in regulating calcium metabolism in vivo. The fluorine atom introduced at the 24-position of either 1,25-(OH) 2 D 2 or its 24-epimer had no potentiating effect. This is in sharp contrast with the cases of 24- and 26,27-multifluorinated analogs of active vitamin D-3.