A series of steroidal compds. were synthesized in order to evaluate the possible influence of the configuration of a stereocenter in the 17beta-side chain on the inhibitory activity on the enzyme 5alpha-reductase (5AR). For this purpose diastereomerically pure 4-azasteroids epimers at C-22 were prepd. (compds. 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 biol. activity. We also considered, for the tested mols., a series of chemico-phys. parameters in order to find a possible correlation with their biol. 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 17beta-side chain.
|Titolo:||Substrate interaction with 5 alpha-reductase enzyme: influence of the 17 beta-chain chirality in the mechanism of action of 4-azasteroid inhibitors|
|Autori interni:||CELOTTI, FABIO MARIA (Ultimo)|
MANZOCCHI, ADA GIOVANNA
|Parole Chiave:||4-Azasteroids;Testosterone 5alpha reductase; Inhibitors; Molecular modeling; Chilarity; Biological activity|
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
Settore MED/04 - Patologia Generale
|Data di pubblicazione:||nov-2001|
|Digital Object Identifier (DOI):||10.1016/S0039-128X(01)00114-3|
|Appare nelle tipologie:||01 - Articolo su periodico|
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