title: Effect of dehydroepiandrosterone derivatives on the activity of 5α-reductase isoenzymes and on cancer cell line PC-3.
abstract: It is well known that testosterone (T) under the influence of 5α-reductase enzyme is converted to dihydrotestosterone (DHT), which causes androgen-dependent diseases. The aim of this study was to synthesize new dehydroepiandrosterone derivatives (3a-e, 4a-i, 6 and 7) having potential inhibitory activity against the 5α-reductase enzyme. This paper also reports the in vivo pharmacological effect of these steroidal molecules. The results from this study showed that all compounds exhibited low inhibitory activity for 5α-reductase type 1 and 2 enzymes and they failed to bind to the androgen receptor. Furthermore, in the in vivo experiment, steroids 3b, 4f, and 4 g showed comparable antiandrogenic activity to that of finasteride; only derivatives 4d and 7 produced a considerable decrease in the weight of the prostate gland of gonadectomized hamsters treated with (T). On the other hand, compounds 4a, f and h showed 100% inhibition of the growth of prostate cancer cell line PC-3, with compound 4 g having a 98.2% antiproliferative effect at 50 μM. The overall data indicated that these steroidal molecules, having an aromatic ester moiety at C-3 (4f-h), could have anticancer properties.
authors.affiliation: Department of Pharmacy, Faculty of Chemistry, National University of Mexico, Mexico, D.F., Mexico.
authors.forename: Eugene
authors.initials: E
authors.lastname: Bratoeff
authors.affiliation: Department of Pharmacy, Faculty of Chemistry, National University of Mexico, Mexico, D.F., Mexico.
authors.forename: Mariana
authors.initials: M
authors.lastname: Garrido
authors.affiliation: Institute of Chemistry, National University of Mexico, Mexico, D.F., Mexico.
authors.forename: Teresa
authors.initials: T
authors.lastname: Ramírez-Apan
authors.affiliation: Department of Biological Systems and Agricultural and Animal Production, Metropolitan University-Xochimilco, Mexico, D.F., Mexico.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Heuze
authors.affiliation: Department of Biological Systems and Agricultural and Animal Production, Metropolitan University-Xochimilco, Mexico, D.F., Mexico.
authors.forename: Araceli
authors.initials: A
authors.lastname: Sánchez
authors.affiliation: Department of Pathology, General Hospital, Mexico, D.F., Mexico.
authors.forename: Juan
authors.initials: J
authors.lastname: Soriano
authors.affiliation: Department of Pathology, General Hospital, Mexico, D.F., Mexico. Electronic address: marisa@correo.xoc.uam.mx.
authors.forename: Marisa
authors.initials: M
authors.lastname: Cabeza
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D042944:Cholestenone 5 alpha-Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006224:Cricetinae; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D011467:Prostate / Q000187:drug effects / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D007527:Isoenzymes; D003687:Dehydroepiandrosterone; D042944:Cholestenone 5 alpha-Reductase
keywords: 5α-Reductase type 1 inhibitors; Benign prostatic hyperplasia; Dehydroepiandrosterone derivatives; Prostate cancer