Abe J, Morikawa M, Miyamoto K, Kaiho S, Fukushima M, Miyaura C, Abe E, Suda T, Nishii Y
Research Laboratories, Chugai Pharmaceutical Co. Ltd., Tokyo, Japan.
FEBS Lett. 1987 Dec 21;226(1):58-62. doi: 10.1016/0014-5793(87)80550-1.
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.
合成了四种在侧链骨架中含有氧原子的维生素D3类似物，以确定它们的诱导分化活性在结构上是否能与其诱导高钙血症的活性相分离。在人髓性白血病细胞（HL-60）中还原硝基蓝四唑的体外效力顺序为：22-氧杂-1α,25-二羟基维生素D3＞1α,25-二羟基维生素D3＞20-氧杂-1α,25-二羟基维生素D3≠22-氧杂-1α-羟基维生素D3＞1α-羟基维生素D3＞20-氧杂-1α-羟基维生素D3。在抑制小鼠骨髓单核细胞白血病细胞（WEHI-3）增殖和诱导分化方面，22-氧杂-1α,25-二羟基维生素D3的效力也比1α,25-二羟基维生素D3高约10倍，但在诱导预先标记的胎鼠颅骨释放45Ca方面，前者比后者弱得多。这些结果表明，维生素D化合物的诱导分化活性在结构上可以与其诱导高钙血症的活性相分离。
