Binding of bis-beta-chloroethylamine derivatives of synthetic estrogens to proteins: dependence on the chemical structure.
We studied binding of 10 new bis-beta-chloroethylamine derivatives of synthetic estrogens of different chemical structure to estradiol receptors in cytosolic fraction of breast carcinoma tissue and to blood plasma proteins. 11alpha-derivatives of estrone and ethynylestradiol with bis-beta-chloroethylamine radical at the 3-position were most potent, while 11beta-substances with the cytostatic residue in this position less effectively competed with labeled estradiol for estradiol receptors. Estrone derivatives with cytostatic residue at the 3-position bound primarily to serum albumin. Ethynylestradiol derivatives with cytostatic residue at the 3-position of the steroid nucleus bound to plasma globulins. Cytostatic radical at the 11-position changed spatial conformation of estrogen cytostatics and they lost their ability to interact with estradiol receptors and blood plasma proteins.
Mayatskaya
E E
EE
Department of Molecular Pharmacology and Radiobiology, Russian State Medical University, Moscow, Russia.
Semeikin
A V
AV
Rzheznikov
V M
VM
Shimanovskii
N L
NL
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D001798:Blood Proteins / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D045166:Estradiol Congeners / Q000737:chemistry* / Q000494:pharmacology*; D005260:Female; D006801:Humans; D015394:Molecular Structure; D051381:Rats; D011959:Receptors, Estradiol / Q000378:metabolism; D012015:Reference Standards; D013329:Structure-Activity Relationship
D018931:Antineoplastic Agents, Hormonal; D001798:Blood Proteins; D045166:Estradiol Congeners; D011959:Receptors, Estradiol