Fernández Susana, Ferrero Miguel
Departamento de Química Orgánica e Inorgánica, Universidad de Oviedo, 33006 Oviedo, Asturias, Spain.
Pharmaceuticals (Basel). 2020 Jul 22;13(8):159. doi: 10.3390/ph13080159.
1α,25-Dihydroxyvitamin D [1α,25-(OH)-D], the hormonally active form of vitamin D, classically regulates bone formation, calcium, and phosphate homeostasis. In addition, this hormone also exerts non-classical effects in a wide variety of target tissues and cell types, such as inhibition of the proliferation and stimulation of the differentiation of normal and malignant cells. However, to produce these actions, supraphysiological doses are required resulting in calcemic effects that limit the use of this natural hormone. During the past 30 years, many structurally modified analogs of the 1α,25-(OH)-D have been synthesized in order to find derivatives that can dissociate the beneficial antiproliferative effects from undesired calcemic effects. Among these candidates, 1α,25-(OH)-19--D analogs have shown promise as good derivatives since they show equal or better activity relative to the parent hormone but with reduced calcemic effects. In this review, we describe the synthetic strategies to obtain the 19--D derivatives and briefly describe their physiological activities.
1α,25-二羟基维生素D [1α,25-(OH)-D] 是维生素D的激素活性形式，传统上调节骨形成、钙和磷的稳态。此外，这种激素还在多种靶组织和细胞类型中发挥非经典作用，如抑制正常细胞和恶性细胞的增殖并刺激其分化。然而，要产生这些作用，需要超生理剂量，这会导致血钙升高的效应，限制了这种天然激素的使用。在过去30年中，人们合成了许多1α,25-(OH)-D的结构修饰类似物，以寻找能够将有益的抗增殖作用与不良的血钙升高作用分离的衍生物。在这些候选物中，1α,25-(OH)-19- -D类似物显示出有望成为良好的衍生物，因为它们相对于母体激素表现出同等或更好的活性，但血钙升高作用减弱。在这篇综述中，我们描述了获得19- -D衍生物的合成策略，并简要描述了它们的生理活性。
