Abstract
We designed by docking and synthesized two novel analogues of 1α,25-dihydroxyvitamin D(3) hydroxymethylated at C-26 (2 and 3). The syntheses were carried out by the convergent Wittig-Horner approach via epoxide 12a as a common key intermediate. The antiproliferative and transactivation potency of the compounds was evaluated in colon and breast cancer cell lines. The analogues showed a similar but reduced activity compared to 1,25(OH)(2)D(3). Analogue 3 was more potent than analogue 2, and in some assays it exhibited potency similar to that of the natural ligand.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antineoplastic Agents / chemical synthesis*
-
Antineoplastic Agents / chemistry
-
Antineoplastic Agents / pharmacology*
-
Breast Neoplasms / drug therapy
-
COS Cells
-
Cell Line, Tumor
-
Cell Proliferation / drug effects*
-
Chlorocebus aethiops
-
Cholecalciferol / analogs & derivatives*
-
Cholecalciferol / chemical synthesis
-
Cholecalciferol / chemistry
-
Cholecalciferol / pharmacology
-
Colonic Neoplasms / drug therapy
-
Drug Design
-
Female
-
Humans
-
Ligands
-
Protein Binding
-
Receptors, Calcitriol / genetics
-
Receptors, Calcitriol / metabolism
Substances
-
1,25-dihydroxy-26-(hydroxymethyl)-26-methylvitamin D3
-
1,25-dihydroxy-26-(hydroxymethyl)vitamin D3
-
Antineoplastic Agents
-
Ligands
-
Receptors, Calcitriol
-
Cholecalciferol