부산대학교 도서관

A newly synthesized fluorinated analogue of 1,25-dihydroxyvatimin D3(1,25(OH)2D3), 26,26,26,27,27, 27-hexafluoro-1,25-dihydroxyvitamin D3(26,27-F6-1,25-(OH)2D3) has been compared with 1,25(OH)2D3as to its biological activity in vitamin D-deficient chicks. One day old, white Leghorn cockerels were fed a rachitogenic diet for 5 weeks. They were then given vehicle or 32.5, 130 or 325 pmol of 26,27-F6-1,25(OH)2D3or 1,25(OH)2D3in a solution of propylenglycol:ethanol (95:5 v/v) sc every day for 2 weeks. Twenty-four hours after the last dose, the animals were sacrificed and their femurs were removed. 26,27-F6-1,25(OH)2D3was more active than 1,25(OH)2D3in stimulating growth, healing of rachitic cartilage visualized by soft X-ray radiography, elevation of serum inorganic phosphorus, and mineralization of rachitic bone. These biological differences between two compounds were observed only for the dose of 130 pmol. However, this fluorinated compound has less binding ability than 1,25(OH)2D3to fetal chick intestinal cytosol receptors. The mechanism of the higher potency of this analogue is still unknown, but its affinity to the 1,25(OH)2D3receptor does not account for the higher activity. Since 26-hydroxylation can be postulated as the inactivation step in vitamin D metabolism, these results suggest that the reason for increased activity of this fluorinated analogue is most likely its slower metabolism.