Synthesis of chimeric 7alpha-substituted estradiol derivatives linked to cholesterol and cholesterylamine.
We report the synthesis of 7alpha-substituted beta-estradiol derivatives bearing side chains terminated with cholesterol and 3beta-cholesterylamine. These chimeric compounds were designed to exhibit high affinity for estrogen receptors (ERs) and cellular plasma membranes to potentially enable regulated uptake of ERs by mammalian cells. Evaluation with recombinant yeast reporting compound-mediated ER dimerization revealed potencies similar to the antiestrogen ICI 182780. Compounds that efficiently deliver dominant negative ERs into cells may provide novel therapeutics against breast cancers.
Hussey
Stephen L
SL
Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, USA.
He
Enfei
E
Peterson
Blake R
BR
D000818:Animals; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000737:chemistry*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism
D011960:Receptors, Estrogen; C072855:cholesterylamine; D004958:Estradiol; D002784:Cholesterol