title: The biological activity of 23-oxa-, 23-oxa-24-oxo-, and 23-thia-dihydroxyvitamin D3.
abstract: Three analogs of 1 alpha,25-(OH)2D3 with an oxygen or another heteroatom at position 23 were synthesized in search of separating the cell-differentiating from the calcemic effects of the vitamin D hormone. Their ability to induce superoxide production in human myeloid leukemia cells (HL-60) was 1 alpha,25-(OH)2D3 > 23-oxa-24-oxo-1 alpha,25-(OH)2D3 > 23-thia-1 alpha,25-(OH)2D3 > 23-oxa-1 alpha, 25-(OH)2D3. 23-oxa-24-oxo-1 alpha, 25(OH)2D3 was slightly more potent than 1 alpha,25-(OH)2D3 in inhibiting cell proliferation in MCF-7 cells and 23-thia- and 23-oxa-1 alpha,25(OH)2D3 were less potent. Their in vitro potency to produce osteocalcin in MG-63 cells was 1 alpha,25-(OH)2D3 > 23-oxa-24-oxo-1 alpha,25-(OH)2D3 > 23-thia-1 alpha,25-(OH)2D3 = 23-oxa-1 alpha,25-(OH)2D3. All three analogs had reduced receptor and DBP affinity compared to 1 alpha,25-(OH)2D3. When these analogs were injected in rachitic chicks, only little calcemic effects were observed. The introduction of a heteroatom in carbon 23 of 1 alpha,25-(OH)2D3 thus creates analogs with dissociated action on cell differentiation and calcium homeostasis.
authors.affiliation: Laboratorium voor Experimentele Geneeskunde en Endocrinologie, K. U. Leuven, Onderwijs en Navorsing Gasthuisberg, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Allewaert
authors.forename: R
authors.initials: R
authors.lastname: Convents
authors.forename: B K
authors.initials: BK
authors.lastname: Tan
authors.forename: S
authors.initials: S
authors.lastname: Marcelis
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.forename: X Y
authors.initials: XY
authors.lastname: Zhao
authors.forename: P
authors.initials: P
authors.lastname: De Clercq
authors.forename: M
authors.initials: M
authors.lastname: Vandewalle
authors.forename: R
authors.initials: R
authors.lastname: Bouillon
mesh_terms: D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D002645:Chickens; D002762:Cholecalciferol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D015675:Osteocalcin / Q000378:metabolism
chemical_list: D015675:Osteocalcin; D002762:Cholecalciferol; D002118:Calcium