Síntesis y evaluación in silico e in vitro de derivados del ácido valproico como antineoplásicos

Abstract

Histone deacetylases are a group of enzymes that are characterized for catalyzing the separation of the acetyl group of the acetylated lysines on histones. This has an effect of compaction of genetic material involved in the region deacetilated; and therefore the suppression of gene expression. The role of these enzymes is aberrant in tumor cells. On the other hand, it was found that valproic acid inhibits this enzyme group, promoting the expression of genes suppressed in tumor cells, causing cell cycle arrest and / or apoptosis. Our team proposed an in silico evaluation of a series of valproic acid derivatives, and from the results the synthesis and evaluation of those derivatives with best interaction predicted values. A derivative was synthesized and characterized following the virtual screening and then it was evaluated in cell cultures of cervical cancer and rhabdomyosarcoma, looking for changes in proliferation, cell viability and apoptosis. Finally, cells from cervical cancer were treated with the derivative and VPA, we extracted the RNA and expression microarrays were performed to characterize the change in the expression profile of tumor cells, caused by the treatment.