Allewaert K, Convents R, Tan B K, Marcelis S, Zhao J, Zhao X Y, De Clercq P, Vandewalle M, Bouillon R
Laboratorium voor Experimentele Geneeskunde en Endocrinologie, K. U. Leuven, Onderwijs en Navorsing Gasthuisberg, Belgium.
Steroids. 1994 Dec;59(12):686-90. doi: 10.1016/0039-128x(94)90099-x.
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.
合成了1α,25-(OH)₂D₃在23位带有氧原子或其他杂原子的三种类似物，以寻求将维生素D激素的细胞分化作用与血钙作用区分开来。它们在人髓系白血病细胞（HL-60）中诱导超氧化物产生的能力为1α,25-(OH)₂D₃ > 23-氧杂-24-氧代-1α,25-(OH)₂D₃ > 23-硫杂-1α,25-(OH)₂D₃ > 23-氧杂-1α,25-(OH)₂D₃。23-氧杂-24-氧代-1α,25(OH)₂D₃在抑制MCF-7细胞增殖方面比1α,25-(OH)₂D₃稍强，而23-硫杂-和23-氧杂-1α,25(OH)₂D₃则较弱。它们在MG-63细胞中产生骨钙素的体外效力为1α,25-(OH)₂D₃ > 23-氧杂-24-氧代-1α,25-(OH)₂D₃ > 23-硫杂-1α,25-(OH)₂D₃ = 23-氧杂-1α,25-(OH)₂D₃。与1α,25-(OH)₂D₃相比，所有三种类似物的受体和DBP亲和力均降低。当将这些类似物注射到佝偻病雏鸡中时，仅观察到轻微的血钙作用。因此，在1α,25-(OH)₂D₃的23位碳原子上引入杂原子可产生对细胞分化和钙稳态具有解离作用的类似物。
