ANTAGONISTIC ACTIVITY OF 24-OXA-ANALOGS OF VITAMIN-D

24-Oxa-vitamin D-3 (24-oxa-D-3) and 24-oxa-1 alpha-hydroxyvitamin D-3 were designed as possible inhibitors of the vitamin D metabolic activa tion pathway. Their affinity for the vitamin D receptor (from pig inte stine) and human vitamin binding protein were reduced, and their poten cy to induce cell differentiation of human leukemia cells (HL 60) or o steosarcoma cells (MG 63) was markedly reduced (19% and 3%, respective ly), in comparison with calcitriol. A single or chronic injection of 2 4-oxa-D-3 had no biological activity, whereas chronic administration o f 24-oxa-1 alpha-hydroxy-D-3 showed weak agonist activity in rachitic chicks. When the 24-oxa-D-3 was given prior to a single injection of v itamin D-3, lower values of serum calcium (64% of the value obtained i n vitamin D-treated animals), osteocalcin (52%), 25-(OH)D-3 (45%) and duodenal calbindin-D 28K (9.4%) were found. When given chronically in a 100-fold more excess no clear antagonistic effects were observed. 24 -0xa-D-3 is thus a new metabolic weak antagonist of vitamin D-3, but a dding a hydroxyl group at C-1 creates a weak agonist.