RESUMEN

The new histone deacylases inhibitors (HDACi) were synthesized in the class of 5-membered cyclic hydroxamic acids (5-CHA), showing medium size CHA as a new Zn-binding group. New reaction sequence was proposed for the synthesis of 5-membered alkylidene-cyclic-hydroxamic acids starting from butyrolactone. Compound 10c showed low µM activity on HeLa cell extracts. From these results, cyclic hydroxamic acids will be further investigated to find more potent compounds.

Asunto(s)

Ácidos Heterocíclicos/síntesis química , Diseño de Fármacos , Inhibidores de Histona Desacetilasas/síntesis química , Ácidos Hidroxámicos/síntesis química , Ácidos Heterocíclicos/química , Ácidos Heterocíclicos/farmacología , Relación Dosis-Respuesta a Droga , Células HeLa , Inhibidores de Histona Desacetilasas/química , Inhibidores de Histona Desacetilasas/farmacología , Humanos , Ácidos Hidroxámicos/química , Ácidos Hidroxámicos/farmacología , Estructura Molecular , Relación Estructura-Actividad