Studies on the Physiological Activities of Novel Vitamin D_3 Derivatives

本文合成了两种新型维生素D_3衍生物：22-氧杂-1，25-二羟基维生素D_3（oxacalcitriol：OCT）和2 β-羟丙氧基-1，25-二羟基维生素D_3（Hydroxypropoxycalcitriol：HCT），并研究了它们的生理活性。结果表明：OCT在体外骨吸收方面与1，25-D_3相似，但在体内钙代谢方面与1，25-D_3不同，OCT对钙代谢无明显影响。由于OCT具有与1，25-D_3相似的诱导白血病细胞向正常巨噬细胞分化的活性，因此它是治疗白血病和其他钙源性疾病而不引起高钙血症的一种有希望的候选药物。25-D_3比1，25-D_3对血浆维生素D结合蛋白的作用更强。对去卵巢大鼠骨丢失的防治作用研究表明，HCT对骨质疏松前期和骨质疏松症模型大鼠骨密度和骨机械强度的改善作用优于1，25-D_3。结果表明，HCT是治疗骨质疏松症的一种有前途的候选药物。

We have synthesized the two novel vitamin D_3 derivatives, 22-oxa-1,25-dihydroxyvitamin D_3 (oxacalcitriol : OCT) and 2beta-hydroxypropoxy-1,25-dihydroxy-vitamin D_3 (Hydroxypropoxycalcitriol : HCT), and studied their physiological activities. The results are summarized in the following ;.Although OCT behaved similar to 1,25-dihydroxyvitamin D_3 (1,25-D_3) in the in vitro bone resorption, it did not give response in the in vivo calcemic activities which were different from 1,25-D_3. Since OCT shows similar activity to 1,25-D_3 in inducing differentiation of leukemia cells to normal macrophage cells, it is a promising candidate for treatment of leukemia and other calcinogenic diseases without causing hypercalcemia.2.We have established a method for the determination of HCT in plasma and found that the half-life of HCT in blood is longer than that of 1,25-D_3 because of stronger vinding to plasma vitamin D binding protein than 1,25-D_3. We have also studied the preventive and therapeutic effects on bone mineral loss in ovariectomized rats and showed that HCT improved bone mineral density and mechanical bone strength in the pre-osteoporosis and osteoprosis model rats made by ovariectomy more effectively than 1,25-D_3. The results suggest that HCT is a promising candidate for treatment of osteoporosis.