Bischof M G, Redlich K, Schiller C, Chirayath M V, Uskokovic M, Peterlik M, Cross H S
Department of General and Experimental Pathology, University of Vienna Medical School, Austria.
J Pharmacol Exp Ther. 1995 Dec;275(3):1254-60.
A panel of synthetic analogs of 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3] bearing one or multiple structural modifications at functionally or metabolically sensitive positions of the molecule, i.e., C-1, 16, 23, 26 and 27, were tested for their growth inhibitory and prodifferentiating potency in human colon adenocarcinoma-derived Caco-2 cells. With respect to the peak response elicited at 10(-8) M, 1 alpha,25-dihydroxy-16-ene-vitamin D3, 1 alpha,25-dihydroxy-23-yne-vitamin D3 and 1 alpha,25-dihydroxy-16,23Z-diene-vitamin D3 suppressed [3H]thymidine incorporation in confluent Caco-2 cells less than 1 alpha,25(OH)2D3. 1 alpha,25-dihydroxy-16,23e-diene-vitamin D3 was at least equipotent to the parent compound, whereas 1 alpha,25-dihydroxy-16-ene-23-yne-vitamin D3 and most conspicuously 1 alpha,25-dihydroxy-26,27-hexafluoro-16-ene-23-yne- vitamin D3 reduced growth of Caco-2 cells to significantly (P < .05) lower levels than 1 alpha,25(OH)2D3. The same rank order was obtained for the ability of the vitamin D compounds to induce activity of the differentiation marker enzyme, alkaline phosphatase, in quiescent Caco-2 cells. Whereas the effect of the synthetic analogs on calcium uptake by cultured embryonic chick duodenum in general was less pronounced than that of 1 alpha,25(OH)2D3, the two most potent antimitogenic compounds, 1 alpha,25-dihydroxy-16-ene-23-yne-vitamin D3 and 1 alpha,25-dihydroxy-26,27-hexafluoro-16-ene-23-yne-vitamin D3, elicited calcium mobilization from cultured neonatal mouse calvaria at a 10-fold lower concentration than the parent compound.(ABSTRACT TRUNCATED AT 250 WORDS)
对一组1α,25 - 二羟基维生素D3 [1α,25(OH)2D3]的合成类似物进行了测试，这些类似物在分子的功能或代谢敏感位置（即C - 1、16、23、26和27）带有一个或多个结构修饰，检测它们在人结肠腺癌来源的Caco - 2细胞中的生长抑制和促分化能力。相对于在10(-8) M时引发的峰值反应，1α,25 - 二羟基 - 16 - 烯 - 维生素D3、1α,25 - 二羟基 - 23 - 炔 - 维生素D3和1α,25 - 二羟基 - 16,23Z - 二烯 - 维生素D3对汇合的Caco - 2细胞中[3H]胸苷掺入的抑制作用小于1α,25(OH)2D3。1α,25 - 二羟基 - 16,23e - 二烯 - 维生素D3至少与母体化合物等效，而1α,25 - 二羟基 - 16 - 烯 - 23 - 炔 - 维生素D3，最显著的是1α,25 - 二羟基 - 26,27 - 六氟 - 16 - 烯 - 23 - 炔 - 维生素D3，使Caco - 2细胞的生长降低到比1α,25(OH)2D3显著（P <.05）更低的水平。对于维生素D化合物在静止的Caco - 2细胞中诱导分化标志物酶碱性磷酸酶活性的能力，也得到了相同的排名顺序。虽然合成类似物对培养的胚胎鸡十二指肠钙摄取的影响一般不如1α,25(OH)2D3明显，但两种最有效的抗有丝分裂化合物，1α,25 - 二羟基 - 16 - 烯 - 23 - 炔 - 维生素D3和1α,25 - 二羟基 - 26,27 - 六氟 - 16 - 烯 - 23 - 炔 - 维生素D3，在比母体化合物低10倍的浓度下就能引起培养的新生小鼠颅骨的钙动员。（摘要截断于250字）
