title: Synthesis and preliminary evaluation of a modified estradiol-core bearing a fused γ-lactone as non-estrogenic inhibitor of 17β-hydroxysteroid dehydrogenase type 1.
abstract: A non-estrogenic inhibitor of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) was designed based on a modified 3-hydroxy-estra-1,3,5(10)-triene core having an additional five-member lactone ring and a benzamide group. The inhibitor was synthesized, fully characterized and tested for its ability to inhibit the enzyme activity. Estrogenicity was also investigated and tested on estrogen-dependent T-47D cell line. Interestingly, this steroid derivative showed inhibitory potency towards 17β-HSD1 and did not present residual unwanted estrogenic activity.
authors.affiliation: Laboratory of Medicinal Chemistry, CHUQ - Research Center and Laval University, 2705 Laurier Blvd., Québec, Canada G1V 4G2.
authors.forename: Etienne
authors.initials: E
authors.lastname: Ouellet
authors.forename: Diana
authors.initials: D
authors.lastname: Ayan
authors.forename: Donald
authors.initials: D
authors.lastname: Poirier
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004958:Estradiol / Q000737:chemistry*; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D007783:Lactones; D004958:Estradiol; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase