Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Design, synthesis, and biological evaluation of new raloxifene analogues of improved antagonist activity and endometrial safety
Δημιουργός/Συγγραφέας:	Lambrinidis, George Gouedard, Cedric Stasinopoulou, Sotiria Angelopoulou, Angeliki [EL] Γάνου, Βασιλική[EN] Ganou, Vassiliki Meligova, Aggeliki K [EL] Μήτσιου, Δήμητρα[EN] Mitsiou, Dimitra J. Marakos, Panagiotis Pouli, Nicole Mikros, Emmanuel [EL] Αλέξης, Μιχαήλ Ν.[EN] Alexis, Michael N.
Ημερομηνία:	2021
Γλώσσα:	Αγγλικά
ISSN:	00452068
DOI:	10.1016/j.bioorg.2020.104482
Άλλο:	33272706
Περίληψη:	Raloxifene agonism of estrogen receptor (ER) in post-menopausal endometrium is not negligible. Based on a rational drug design workflow, we synthesized 14 analogues of raloxifene bearing a polar group in the aromatic ring of the basic side chain (BSC) and/or changes in the bulkiness of the BSC amino group. Analogues with a polar BSC aromatic ring and amino group substituents of increasing volume displayed increasing ER antagonism in Ishikawa cells. Analogues with cyclohexylaminoethoxy (13a) or adamantylaminoethoxy BSC (13b) lacking a polar aromatic ring displayed high ER-binding affinity and ER antagonism in Ishikawa cells higher than raloxifene and similar to fulvestrant (ICI182,780). The endometrial surface epithelium of immature female CD1 mice injected with 13b was comparable to that of vehicle-treated mice, while that of mice treated with estradiol, raloxifene or 13b in combination with estradiol was hyperplastic. These findings indicate that raloxifene analogues with a bulky BSC amino group could provide for higher endometrial safety treatment of the menopausal syndrome.
Τίτλος πηγής δημοσίευσης:	Bioorganic chemistry
Τόμος/Κεφάλαιο:	106
Σελίδες:	104482
Θεματική Κατηγορία:	[EL] Βιοχημεία[EN] Biochemistry
Λέξεις-Κλειδιά:	Drug design Endometrial safety Estrogen receptors Hormones Raloxifene SERMs Animals Dose-Response Relationship, Drug Endometrium Estrogen Antagonists Female Mice Molecular Structure Raloxifene Hydrochloride Receptors, Estrogen Structure-Activity Relationship Drug Design
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο