title: First synthesis of 7alpha- and 7beta-amino-DHEA, dehydroepiandrosterone (DHEA) analogues and preliminary evaluation of their cytotoxicity on Leydig cells and TM4 Sertoli cells.
abstract: Efficient syntheses of new DHEA analogues, and their apoptotic and necrotic effects on Leydig cells and TM4 Sertoli cells are described. The key step in the synthetic strategy of 7-amino-DHEA derivatives involves a bromination on C-7 position to give an epimeric mixture of bromides which were substituted by azides and reduced to give 7alpha- and 7beta-amino-3beta-hydroxyandrost-5-en-17-ones. No cytotoxic effect induced by apoptosis mechanism was observed on Leydig and TM4 Sertoli cells by treatment with these amino-DHEA analogues. A necrotic effect was induced only in TM4 Sertoli cells. The best activity was obtained with 7alpha,beta-amino-androst-5-en-3beta-ol and 7beta-amino-3beta-hydroxy-androst-5-en-17-one.
authors.affiliation: Centre d'Etudes et de Recherche sur le Médicament de Normandie, UFR des Sciences Pharmaceutiques, Caen cedex, France.
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Bazin
authors.forename: Carine
authors.initials: C
authors.lastname: Travert
authors.forename: Serge
authors.initials: S
authors.lastname: Carreau
authors.forename: Sylvain
authors.initials: S
authors.lastname: Rault
authors.forename: Laïla
authors.initials: L
authors.lastname: El Kihel
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D007985:Leydig Cells / Q000187:drug effects*; D008297:Male; D008968:Molecular Conformation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012708:Sertoli Cells / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C520295:7alpha-amino-dehydroepiandrosterone; D003687:Dehydroepiandrosterone