Premium
Synthesis, Structure, and Biological Activity of des‐Side Chain Analogues of 1α,25‐Dihydroxyvitamin D 3 with Substituents at C18
Author(s) -
Verlinden Lieve,
Verstuyf Annemieke,
Eelen Guy,
Bouillon Roger,
OrdóñezMorán Paloma,
Larriba María Jesús,
Muñoz Alberto,
Rochel Natacha,
Sato Yoshiteru,
Moras Dino,
Maestro Miguel,
Seoane Samuel,
Dominguez Fernando,
EduardoCanosa Silvina,
Nicoletti Daniel,
Moman Edelmiro,
Mouriño Antonio
Publication year - 2011
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201100021
Subject(s) - side chain , calcitriol receptor , chemistry , stereochemistry , vitamin d and neurology , biological activity , receptor , structure–activity relationship , biochemistry , in vitro , biology , endocrinology , organic chemistry , polymer
An improved synthetic route to 1α,25‐dihydroxyvitamin D 3 des‐side chain analogues 2 a and 2 b with substituents at C18 is reported, along with their biological activity. These analogues display significant antiproliferative effects toward MCF‐7 breast cancer cells and prodifferentiation activity toward SW480‐ADH colon cancer cells; they are also characterized by a greatly decreased calcemic profile. The crystal structure of the human vitamin D receptor (hVDR) complexed to one of these analogues, 20(17→18)‐abeo‐1α,25‐dihydroxy‐22‐homo‐21‐norvitamin D 3 ( 2 a ) reveals that the side chain introduced at position C18 adopts the same orientation in the ligand binding pocket as the side chain of 1α,25‐dihydroxyvitamin D 3 .