title: Synthesis of a dansyl-labeled inhibitor of 17β-hydroxysteroid dehydrogenase type 3 for optical imaging.
abstract: The steroidogenic enzyme 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) is a therapeutic target in the management of androgen-sensitive diseases such as prostate cancer and benign prostate hyperplasia. In this Letter, we designed and synthesized the first fluorescent inhibitor of this enzyme by combining a fluorogenic dansyl moiety to the chemical structure of a known inhibitor of 17β-HSD3. The synthesized compound 3 is a potent fluorogenic compound (λex=348 nm and λ em=498 nm). It crosses the cell membrane, keeps its fluorescent properties and is distributed inside the LNCaP cells overexpressing 17β-HSD3, where it inhibits the transformation of 4-androstene-3,17-dione into the androgen testosterone (IC50=262 nM).
authors.affiliation: Laboratory of Medicinal Chemistry, CHU de Québec-Research Center (CHUL, T4-42), 2705 Laurier Boulevard, Québec (Québec) G1V 4G2, Canada.
authors.forename: Lucie Carolle
authors.initials: LC
authors.lastname: Kenmogne
authors.affiliation: Laboratory of Medicinal Chemistry, CHU de Québec-Research Center (CHUL, T4-42), 2705 Laurier Boulevard, Québec (Québec) G1V 4G2, Canada.
authors.forename: René
authors.initials: R
authors.lastname: Maltais
authors.affiliation: Laboratory of Medicinal Chemistry, CHU de Québec-Research Center (CHUL, T4-42), 2705 Laurier Boulevard, Québec (Québec) G1V 4G2, Canada; Department of Molecular Medicine, Faculty of Medicine, Université Laval, Québec (Québec), Canada. Electronic address: donald.poirier@crchul.ulaval.ca.
authors.forename: Donald
authors.initials: D
authors.lastname: Poirier
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D000731:Androstanes / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D003619:Dansyl Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D013449:Sulfonamides / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000731:Androstanes; D003619:Dansyl Compounds; D005456:Fluorescent Dyes; D013449:Sulfonamides; D015067:17-Hydroxysteroid Dehydrogenases; C476565:17beta-hydroxysteroid dehydrogenase type 3
keywords: Dansyl; Fluorescent agent; Hydroxysteroid dehydrogenase; Inhibitor; Steroid