Substrate interaction with 5α-reductase enzyme: Influence of the 17β-chain chirality in the mechanism of action of 4-azasteroid inhibitors
Articolo
Data di Pubblicazione:
2001
Citazione:
Substrate interaction with 5α-reductase enzyme: Influence of the 17β-chain chirality in the mechanism of action of 4-azasteroid inhibitors / P. Grisenti, A. Magni, V. Olgiati, A. Manzocchi, P. Ferraboschi, V. Villani, R. Pucciariello, F. Celotti. - In: STEROIDS. - ISSN 0039-128X. - 66:11(2001), pp. 803-810.
Abstract:
A series of steroidal compounds were synthesized in order to evaluate the possible influence of the configuration of a stereocenter in the 17β-side chain on the inhibitory activity on the enzyme 5α-reductase (5AR). For this purpose diastereomerically pure 4-azasteroids epimers at C-22 were prepared (compounds 1-11) and tested as inhibitors of 5AR in 'in vitro' tests. The obtained data showed that in most cases the couples of epimers possess a significant difference in their biological activity. We also considered, for the tested molecules, a series of chemico-physical parameters in order to find a possible correlation with their biological activity. The findings allowed us to propose a model of the binding site of 5AR which comprises also, for 4-azasteroid inhibitors, the configurational aspect of the 17β-side chain.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
4-azasteroids; testosterone 5 alpha reductase; inhibitors; molecular modeling; chirality; biological activity
Elenco autori:
P. Grisenti, A. Magni, V. Olgiati, A. Manzocchi, P. Ferraboschi, V. Villani, R. Pucciariello, F. Celotti
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