Effect on Carbon Lengthening at the Side Chain Terminal of 1α, 25-Dihydroxyvitamin D₃ for Calcium Regulating Activity

Abstract

A series of analogs of 1α, 25-dihydroxyvitamin D₃ [1, 25-(OH)₂D₃ (1)] with alkyl substitutions in 26- and 27- positions have been tested for their activity 1) in competing with 1, 25-(OH)₂D₃ for binding to chick intestinal cytosol receptor, 2) in ability for formation of multinucleated cells (MNC) with various osteoclastic cell characteristics from blast cells, and 3) in stimulating bone calcium mobilization in vitamin D-deficient rats. The relative potencies of 1, 25-(OH)₂D₃, 1α, 25-dihydroxy-26, 27-dimethylvitamin D₃ (2), 1α, 25-dihydroxy-26, 27-diethylvitamin D₃ (3), and 1α, 25-dihydroxy-26, 27-dipropylvitamin D₃ (4) in competing for intestinal cytosolic binding were 1 : 1.1 : 0.25 : 0.05. The similar order of the abilities on formation of the multinucleated cells in the same series was observed. In a bone calcium mobilization test with vitamin D-deficient rats, 1α, 25-dihydroxy-26, 27-dimethylvitamin D₃ showed slightly less activity than 1, 25-(OH)₂D₃ at 12h after administration, but long lasting activity was observed during time course experiments. 1α, 25-Dihydroxy-26, 27-diethylvitamin D₃, and 1α, 25-dihydroxy-26, 27-dipropylvitamin D₃ were found to be much less active than 1, 25(OH)₂D₃ in a bone calcium mobilization test.