RESUMEN

A series of new HIV-1 protease inhibitors with the hydroxyethylamine core and different hydroxyprolinamide P2 ligands were designed and synthesized. Variation of substitutions at the P2 significantly affected the enzyme inhibitory potency of the inhibitors. Compounds 2a and 2d showed excellent enzyme inhibitory activity with IC(50) values in the nanomolar range. An active site binding model for inhibitors 2a and 2d was suggested based upon the computational-docking results of the ligand with HIV-1 protease. This model offers molecular insights regarding ligand-binding site interactions of the hydroxyprolinamide-derived novel P2-ligand.

Asunto(s)

Amidas/síntesis química , Inhibidores de la Proteasa del VIH/síntesis química , VIH-1/enzimología , Hidroxiprolina/síntesis química , Amidas/química , Amidas/farmacología , Sitios de Unión , Darunavir , Diseño de Fármacos , Inhibidores de la Proteasa del VIH/química , Inhibidores de la Proteasa del VIH/farmacología , VIH-1/efectos de los fármacos , Humanos , Hidroxiprolina/química , Hidroxiprolina/farmacología , Concentración 50 Inhibidora , Ligandos , Estructura Molecular , Sulfonamidas/química , Sulfonamidas/farmacología