RESUMEN

New CA(1)A(2)X peptidomimetics are described as Ras farnesyl transferase inhibitors (FTIs). They include cysteine and methionine as mimetics of the C-terminus sequence of farnesylated proteins. Furthermore, cysteine was replaced by heterocycles, taking into account the role of zinc and the metabolic instability of amino acids. The molecular docking of 8 in the active site of the enzyme and the pharmacological evaluation of the compounds are illustrative of a new class of FTIs.

Asunto(s)

Transferasas Alquil y Aril/antagonistas & inhibidores , Inhibidores Enzimáticos/síntesis química , Imidazoles/síntesis química , Péptidos/química , Tiazoles/síntesis química , Células 3T3 , Animales , Permeabilidad de la Membrana Celular , Cisteína/química , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Imidazoles/química , Imidazoles/farmacología , Metionina/química , Ratones , Modelos Moleculares , Imitación Molecular , Relación Estructura-Actividad , Tiazoles/química , Tiazoles/farmacología