24-氟-1α,25-二羟基维生素D-2及其24-差向异构体的生物学活性。

Biological activities of 24-fluoro-1 alpha,25-dihydroxyvitamin D-2 and its 24-epimer.

作者信息

Imae Y, Manaka A, Yoshida N, Ishimi Y, Shinki T, Abe E, Suda T, Konno K, Takayama H, Yamada S

机构信息

Research Laboratories of Biological Science, Kodama Ltd., Chiba, Japan.

出版信息

Biochim Biophys Acta. 1994 Aug 4;1213(3):302-8.

PMID:8049243

Abstract

Biological activities of two epimeric 24-fluorinated vitamin D-2 analogs, 24-fluoro-1 alpha,25-dihydroxyvitamin D-2 [24-F-1,25-(OH)2D2] and its 24-epimer [24-epi-24-F-1,25-(OH)2D2], were studied and compared with 1 alpha,25-dihydroxyvitamin D-3 [1,25-(OH)2D3] and 1 alpha,25-dihydroxyvitamin D-2 [1,25-(OH)2D2]. 24-F-1,25-(OH)2D2 was nearly as active as 1,25-(OH)2D3 and 1,25-(OH)2D2 both in regulating calcium metabolism in vivo including bone mineral mobilization and intestinal calcium transport and in inducing differentiation of HL-60 cells. While 24-epi-24-F-1,25-(OH)2D2 showed distinct properties in these two types of the actions. Though the 24-epimer was nearly as potent as 1,25-(OH)2D3 in inducing differentiation of HL-60 cells, it showed little activity in regulating calcium metabolism in vivo. The fluorine atom introduced at the 24-position of either 1,25-(OH)2D2 or its 24-epimer had no potentiating effect. This is in sharp contrast with the cases of 24- and 26,27-multifluorinated analogs of active vitamin D-3.

摘要

研究了两种差向异构的24-氟维生素D-2类似物，即24-氟-1α,25-二羟基维生素D-2 [24-F-1,25-(OH)2D2]及其24-差向异构体[24-表-24-F-1,25-(OH)2D2]的生物学活性，并与1α,25-二羟基维生素D-3 [1,25-(OH)2D3]和1α,25-二羟基维生素D-2 [1,25-(OH)2D2]进行了比较。24-F-1,25-(OH)2D2在体内调节钙代谢（包括骨矿物质动员和肠道钙转运）以及诱导HL-60细胞分化方面的活性几乎与1,25-(OH)2D3和1,25-(OH)2D2相同。而24-表-24-F-1,25-(OH)2D2在这两种作用中表现出不同的特性。尽管该24-差向异构体在诱导HL-60细胞分化方面的效力几乎与1,25-(OH)2D3相同，但在体内调节钙代谢方面几乎没有活性。在1,25-(OH)2D2或其24-差向异构体的24位引入氟原子没有增强作用。这与活性维生素D-3的24-和26,27-多氟类似物的情况形成鲜明对比。