title: Synthesis and biological evaluation of esters of 16-formyl-17-methoxy-dehydroepiandrosterone derivatives as inhibitors of 5α-reductase type 2.
abstract: In this study, we investigated the in vitro effect of 16-formyl-17-methoxy dehydroepiandrosterone derivatives on the activity of 5α-reductase type 2 (5α-R2) obtained from human prostate. The activity of different concentrations of these derivatives was determined for the conversion of labelled testosterone to dihydrotestosterone. The results indicated that an aliphatic ester moiety at the C-3 position of these derivatives increases their in vitro potency as inhibitors of 5α-R2 activity compared to finasteride®, which is considered to be a potent inhibitor of 5α-R2. In this case, the augmentation of the lipophilicity of these dehydroepiandrosterone derivatives increased their potency as inhibitors of 5α-R2. However, the presence of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl rings as the cycloaliphatic ester moiety at C-3 of the formyl methoxy dehydroepiandrosterone scaffold did not inhibit the activity of this enzyme. This may be due to the presence of steric factors between the enzyme and the spatial structure of these derivatives.
authors.affiliation: a Departamento de Sistemas Biológicos y de Producción Agrícola y Animal , Universidad Autónoma Metropolitana-Xochimilco , México, D.F. , 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 , México, D.F. , México .|b Departamento de Farmacia , Facultad de Química, Universidad Nacional Autónoma de México , México, D.F. , México , and.
authors.forename: Yazmín
authors.initials: Y
authors.lastname: Arellano
authors.affiliation: b Departamento de Farmacia , Facultad de Química, Universidad Nacional Autónoma de México , México, D.F. , México , and.
authors.forename: Eugene
authors.initials: E
authors.lastname: Bratoeff
authors.affiliation: a Departamento de Sistemas Biológicos y de Producción Agrícola y Animal , Universidad Autónoma Metropolitana-Xochimilco , México, D.F. , México .
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Heuze
authors.affiliation: b Departamento de Farmacia , Facultad de Química, Universidad Nacional Autónoma de México , México, D.F. , México , and.
authors.forename: Karen
authors.initials: K
authors.lastname: Córdova
authors.affiliation: b Departamento de Farmacia , Facultad de Química, Universidad Nacional Autónoma de México , México, D.F. , México , and.
authors.forename: Gladys
authors.initials: G
authors.lastname: Nieves
authors.affiliation: c Departamento de Patología , Hospital General de México , México, D.F. , 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 , México, D.F. , México .
authors.forename: Marisa
authors.initials: M
authors.lastname: Cabeza
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000494:pharmacology*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000494:pharmacology*; D006801:Humans; D008297:Male; D066244:Proton Magnetic Resonance Spectroscopy; D016339:Spectrometry, Mass, Fast Atom Bombardment
chemical_list: D058891:5-alpha Reductase Inhibitors; D003687:Dehydroepiandrosterone
keywords: 16-formyl-17-methoxy dehydroepiandrosterone ester derivatives; 5α-Reductase inhibitors; 5α-reductase type 2; androgen receptor; prostate cancer