RESUMEN

The inhibition effects of enantiomerically pure alpha-(N-benzylamino)benzylphosphonic acids and their derivatives on human prostatic acid phosphatase have been investigated. As expected, (R)-alpha-(N-benzylamino)benzylphosphonic acid demonstrated higher affinity for the enzyme than (S)-enantiomer. At the same time, (1R,2S)-phenyl[(1-phenylethyl)amino]methylphosphonic acid was found to be a significantly weaker inhibitor than its (1S,2R)-analogue. The enantioselectivity has been explained using a molecular modeling approach by computational docking of inhibitors into active center of prostatic acid phosphatase.

Asunto(s)

Bencilaminas/síntesis química , Química Farmacéutica/métodos , Organofosfonatos/síntesis química , Inhibidores de Proteasas/farmacología , Proteínas Tirosina Fosfatasas/antagonistas & inhibidores , Proteínas Tirosina Fosfatasas/química , Fosfatasa Ácida , Bencilaminas/farmacología , Diseño de Fármacos , Humanos , Concentración 50 Inhibidora , Masculino , Modelos Químicos , Modelos Moleculares , Conformación Molecular , Organofosfonatos/química , Organofosfonatos/farmacología , Próstata/efectos de los fármacos , Próstata/metabolismo , Unión Proteica , Estereoisomerismo , Termodinámica