title: Synthetic analogues of vitamin D3 with an oxygen atom in the side chain skeleton. A trial of the development of vitamin D compounds which exhibit potent differentiation-inducing activity without inducing hypercalcemia.
abstract: Four analogues of vitamin D3 with an oxygen atom in the side chain skeleton were synthesized to determine whether their differentiation-inducing activity could be separated structurally from their activity to induce hypercalcemia. The order of the in vitro potency to reduce nitroblue tetrazolium in human myeloid leukemia cells (HL-60) was 22-oxa-1 alpha, 25-(OH)2D3 greater than 1 alpha, 25-(OH)2D3 greater than 20-oxa-1 alpha, 25-(OH)2D3 not equal to 22-oxa-1 alpha-(OH)D3 greater than 1 alpha-(OH)D3 greater than 20-oxa-1 alpha-(OH)D3. 22-Oxa-1 alpha, 25-(OH)2D3 was also about 10-times more potent than 1 alpha, 25-(OH)2D3 in suppressing proliferation and inducing differentiation of mouse myelomonocytic leukemia cells (WEHI-3), but the former was much weaker than the latter in inducing the release of 45Ca from prelabeled fetal mouse calvaria. These results suggest that the differentiation-inducing activity of vitamin D compounds can be separated structurally from their activity to induce hypercalcemia.
authors.affiliation: Research Laboratories, Chugai Pharmaceutical Co. Ltd., Tokyo, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Abe
authors.forename: M
authors.initials: M
authors.lastname: Morikawa
authors.forename: K
authors.initials: K
authors.lastname: Miyamoto
authors.forename: S
authors.initials: S
authors.lastname: Kaiho
authors.forename: M
authors.initials: M
authors.lastname: Fukushima
authors.forename: C
authors.initials: C
authors.lastname: Miyaura
authors.forename: E
authors.initials: E
authors.lastname: Abe
authors.forename: T
authors.initials: T
authors.lastname: Suda
authors.forename: Y
authors.initials: Y
authors.lastname: Nishii
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000187:drug effects*; D001842:Bone and Bones / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002762:Cholecalciferol / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D013329:Structure-Activity Relationship
chemical_list: D002762:Cholecalciferol; D002118:Calcium