Biological activity of vitamin D3 derivatives in inducing differentiation of HL-60 human promyelocytic leukemia cells.

Induction of cell differentiation by twenty-one derivatives of vitamin D3 and their binding affinity for the receptor of 1 alpha,25-dihydroxyvitamin D3, an active vitamin D3 metabolite, were examined using HL-60 human promyelocytic leukemia cells and chick intestinal cytosol, respectively. 1 alpha,24(R)-dihydroxy-26-chlorovitamin D3 is found to be more active than 1 alpha,24(R)-dihydroxyvitamin D3 and 1 alpha,25-dihydroxyvitamin D3 in the two abilities to induce the differentiation and to bind to the receptor. The results suggest that a hydroxy group at C-1 position of vitamin D3 and a hydroxy or oxo group at C-25 or C-24 position are essential for both abilities. In diastereoisomers of 1 alpha,25-dihydroxyvitamin D3-26,23-lactone, synthesized (23 S,25 S) 1 alpha,25-dihydroxyvitamin D3-26,23-lactone was more active in both abilities than the natural metabolite, (23 S,25 R) 1 alpha,25-dihydroxyvitamin D3-26,23-lactone, which shows anti-vitamin D action.