Synthesis and biological evaluation of esters of 16-formyl-17-methoxy-dehydroepiandrosterone derivatives as inhibitors of 5α-reductase type 2 |
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Authors: | Araceli Sánchez-Márquez Yazmín Arellano Eugene Bratoeff Yvonne Heuze Karen Córdova Gladys Nieves |
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Institution: | 1. Departamento de Sistemas Biológicos y de Producción Agrícola y Animal, Universidad Autónoma Metropolitana-Xochimilco, México, D.F., México,;2. Departamento de Sistemas Biológicos y de Producción Agrícola y Animal, Universidad Autónoma Metropolitana-Xochimilco, México, D.F., México,;3. Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, México, D.F., México, and;4. Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, México, D.F., México, and |
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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. |
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Keywords: | 5α-Reductase inhibitors 5α-reductase type 2 16-formyl-17-methoxy dehydroepiandrosterone ester derivatives androgen receptor prostate cancer |
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