Current Pharmaceutical Design - Volume 6, Issue 7, 2000

The wide range of activities now attributed to 1,25(OH)2 D 3 has suggested numerous potential therapeutic applications for this vitamin D hormone, including inhibiting growth of various type of cancer. Unfortunately, the potent calcemic activity of the natural hormone has precluded its use in most cases. Vitamin D analogs with higher therapeutic indices offer renewed hope for treatment of malignancies. The promising Read More

The role of 1,25-dihydroxyvitamin D 3 (1,25-(OH)2 D 3 ) as a regulator of cell growth and differentiation is well recognized. Currently, 1,25-(OH)2 D 3 and vitamin D analogs are being evaluated for their therapeutic potential in the treatment of hyperproliferative disorders like cancer. In the present review, we will discuss several processes that might be involved in 1,25-(OH)2 D 3 - and vitamin D analog-mediated suppression Read More

In the first section, the general three-dimensional structure of the ligand-binding domain (LBD) of nuclear receptors (NR) was briefly described on the basis of their x-ray crystal structures. Emphasis was placed on the three major conformations of NR-LBD and their role in the transactivation function. In the second part, the structure-function relationship of vitamin D was analyzed based on the ligand struc-ture, in particular b Read More

Vitamin D analogs in which the triene moiety is replaced by an aromatic ring have been synthesized and their ability to bind to the vitamin D receptor investigated.

The results of our studies on the biological activity of side-chain modified analogues of vitamin D are reviewed. These analogues appeared to be effective in induction of cell differentiation, inhibition of tumour cell proliferation in vitro and in increasing of antitumour effect of cytostatics. On the other hand, inhibition of cytostatic-induced apoptosis by these compounds was observed. The mechanism of the antiproliferative effect Read More

The introduction of oxygen atoms into different positions of the vitamin D side chain is described. By combining the arising 23-oxa and 25-oxa elements with other structural modifications (19-nor, iso-19-nor, 20-methyl, 20-ene, 20,21-cyclo) calcitriol analogs with remarkable levels of dissociation between beneficial acitivities on cell growth regulation and undesired hypercalcemia were identified. Structure-activity relati Read More

Growing interests have been focused on the development of hybrid-analogs with modifications of the A-ring and the side chain of 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3). An exocyclic methylene group at C-10, a hydroxy group at C-1 and a hydroxy group at C-3 play a crucial role in the expression of biological activities of 1alpha,25(OH)2D3. However, relationship between the functional groups and activities ha Read More

In this article are reviewed available experimental and clinical studies on vitamin D analogs, and molecular and cellular mechanisms of their antineoplastic activity. In more detail are discussed the antiproliferative and pro-differentiative effects, inhibition of tumor-induced angiogenesis and induction of apoptosis. The use of vitamin D analogs is however hampered by their toxicity. In various experimental systems it was show Read More