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.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Cell Proliferation/drug effects , Cholecalciferol/analogs & derivatives , Animals , Antineoplastic Agents/chemistry , Breast Neoplasms/drug therapy , COS Cells , Cell Line, Tumor , Chlorocebus aethiops , Cholecalciferol/chemical synthesis , Cholecalciferol/chemistry , Cholecalciferol/pharmacology , Colonic Neoplasms/drug therapy , Drug Design , Female , Humans , Ligands , Protein Binding , Receptors, Calcitriol/genetics , Receptors, Calcitriol/metabolismABSTRACT
Hapten derivatives of 25-hydroxyvitamin D(3) and 1alpha,25-dihydroxyvitamin D(3) were synthesized using the Wittig-Horner approach. Both haptens bearing a carboxylic group at the side chain that can be linked to a protein for raising antibodies of potential utility for the determination of 25-hydroxyvitamin D(3), 1alpha,25-dihydroxyvitamin D(3) and 1alpha-hydroxylated vitamin D(3) analogues.
