57361-81-6Relevant articles and documents
Novel 17 substituted pregnadiene derivatives as 5α-reductase inhibitors and their binding affinity for the androgen receptor
Cabeza, Marisa,Flores, Eugenio,Heuze, Ivonne,Sanchez, Mauricio,Bratoeff, Eugene,Ramirez, Elena,Francolugo, Victor Alfonso
, p. 535 - 539 (2007/10/03)
The in vitro antiandrogenic activity of four new progesterone derivatives: 4, 5, 6 and 7 (8 is a known compound) was determined. These compounds were evaluated as 5α-reductase inhibitors as well as by their capacity to bind to the androgen receptor in gonadectomized hamster prostate. The IC50 value was determined using increasing concentrations of 4, 5, 6, 7 and 8 in the presence of [3H]T and the microsomal fraction of the hamster prostate containing the 5α-reductase enzyme. In this paper we also demonstrated the effect of increasing concentrations of the novel steroids upon [3H]DHT binding to the androgen receptors from hamster prostate which produces competition for the androgen receptor sites. The in vitro studies showed that steroids 4, 5, 6, 7 and 8 had an inhibitory activity for the 5α-reductase with IC50 of: 4 (0.17 μM), 5 (0.19 μM), 6 (1 μM), 7 (4.2 μM), and 8 (2.7 μM). On the other hand, the IC 50 value for compounds 4, 5, 6, 7, 8 and DHT showed the following order of affinity for the androgen receptor: 6>7>5>DHT. Surprisingly compounds 4 and 8 did not bind to the androgen receptor. The overall data indicate that all synthesized compounds are inhibitors for the enzyme 5α-reductase present in the hamster prostate. In contrast, compounds 5, 6 and 7, which have a cyclohexyl group in the side chain showed a high affinity for the androgen receptor.
