title: Synthesis and biological evaluation of 1α,25-dihydroxyvitamin D(3) analogues hydroxymethylated at C-26.
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.
authors.affiliation: Departamento de Química Orgánica y Unidad Asociada al CSIC, Universidad de Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Regueira
authors.forename: Shaonly
authors.initials: S
authors.lastname: Samanta
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Malloy
authors.forename: Paloma
authors.initials: P
authors.lastname: Ordonez-Moran
authors.forename: Diana
authors.initials: D
authors.lastname: Resende
authors.forename: Fredy
authors.initials: F
authors.lastname: Sussman
authors.forename: Alberto
authors.initials: A
authors.lastname: Munoz
authors.forename: Antonio
authors.initials: A
authors.lastname: Mourino
authors.forename: David
authors.initials: D
authors.lastname: Feldman
authors.forename: Mercedes
authors.initials: M
authors.lastname: Torneiro
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy; D019556:COS Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002522:Chlorocebus aethiops; D002762:Cholecalciferol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000188:drug therapy; D015195:Drug Design; D005260:Female; D006801:Humans; D008024:Ligands; D011485:Protein Binding; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism
chemical_list: C560303:1,25-dihydroxy-26-(hydroxymethyl)-26-methylvitamin D3; C560304:1,25-dihydroxy-26-(hydroxymethyl)vitamin D3; D000970:Antineoplastic Agents; D008024:Ligands; D018167:Receptors, Calcitriol; D002762:Cholecalciferol