First synthesis of 7alpha- and 7beta-amino-DHEA, dehydroepiandrosterone (DHEA) analogues and preliminary evaluation of their cytotoxicity on Leydig cells and TM4 Sertoli cells.
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.
Bazin
Marc-Antoine
MA
Centre d'Etudes et de Recherche sur le Médicament de Normandie, UFR des Sciences Pharmaceutiques, Caen cedex, France.
Travert
Carine
C
Carreau
Serge
S
Rault
Sylvain
S
El Kihel
Laïla
L
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
C520295:7alpha-amino-dehydroepiandrosterone; D003687:Dehydroepiandrosterone