title: Novel dehydroepiandrosterone benzimidazolyl derivatives as 5α-reductase isozymes inhibitors.
abstract: 5α-R isozymes (types 1 and 2) play an important role in prostate gland development because they are responsible for intraprostatic dihydrotestosterone (DHT) levels when the physiological serum testosterone (T) concentration is low. In this study, we synthesized seven novel dehydroepiandrosterone derivatives with benzimidazol moiety at C-17, and determined their effect on the activity of 5α-reductase types 1 and 2. The derivatives with an aliphatic ester at C-3 of the dehydroepiandrosterone scaffold induced specific inhibition of 5α-R1 activity, whereas those with a cycloaliphatic ester (cyclopropyl, cyclobutyl, or cyclopentyl ring) or an alcohol group at C-3 inhibited the activity of both isozymes. Derivatives with a cyclohexyl or cycloheptyl ester at C-3 showed no inhibitory activity. In pharmacological experiments, derivatives with esters having an alcohol or the aliphatic group or one of the three smaller cycloaliphatic rings at C-3 decreased the diameter of male hamster flank organs, with the cyclobutyl and cyclopentyl esters exhibiting higher effect. With exception of the cyclobutyl and cyclopentyl esters, these compounds reduced the weight of the prostate and seminal vesicles.
authors.affiliation: a Departamento de Sistemas Biológicos y de Producción Agrícola y Animal , Universidad Autónoma Metropolitana-Xochimilco , Ciudad de México , México.
authors.forename: Yazmín
authors.initials: Y
authors.lastname: Arellano
authors.affiliation: b Facultad de Química, Departamento de Farmacia , Universidad Nacional Autónoma de México, Ciudad de México , Distrito Federal , México , and.
authors.forename: Eugene
authors.initials: E
authors.lastname: Bratoeff
authors.affiliation: b Facultad de Química, Departamento de Farmacia , Universidad Nacional Autónoma de México, Ciudad de México , Distrito Federal , México , and.
authors.forename: Tania
authors.initials: T
authors.lastname: Segura
authors.affiliation: b Facultad de Química, Departamento de Farmacia , Universidad Nacional Autónoma de México, Ciudad de México , Distrito Federal , México , and.
authors.forename: Maria Eugenia
authors.initials: ME
authors.lastname: Mendoza
authors.affiliation: a Departamento de Sistemas Biológicos y de Producción Agrícola y Animal , Universidad Autónoma Metropolitana-Xochimilco , Ciudad de México , México.
authors.forename: Araceli
authors.initials: A
authors.lastname: Sánchez-Márquez
authors.affiliation: a Departamento de Sistemas Biológicos y de Producción Agrícola y Animal , Universidad Autónoma Metropolitana-Xochimilco , Ciudad de México , México.
authors.forename: Yesica
authors.initials: Y
authors.lastname: Medina
authors.affiliation: a Departamento de Sistemas Biológicos y de Producción Agrícola y Animal , Universidad Autónoma Metropolitana-Xochimilco , Ciudad de México , México.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Heuze
authors.affiliation: c Departamento de Patología , Hospital General de México , México.
authors.forename: Juan
authors.initials: J
authors.lastname: Soriano
authors.affiliation: a Departamento de Sistemas Biológicos y de Producción Agrícola y Animal , Universidad Autónoma Metropolitana-Xochimilco , Ciudad de México , México.
authors.forename: Marisa
authors.initials: M
authors.lastname: Cabeza
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D042944:Cholestenone 5 alpha-Reductase / Q000302:isolation & purification / Q000378:metabolism*; D006224:Cricetinae; D003687:Dehydroepiandrosterone / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D058891:5-alpha Reductase Inhibitors; D007527:Isoenzymes; D003687:Dehydroepiandrosterone; D042944:Cholestenone 5 alpha-Reductase
keywords: 5α-R isoenzyme; benign prostatic hyperplasia; dehydroepiandrosterone benzimidazolyl derivative; hamster flank organ; prostate gland