Derivados n-acilhidrazonas como agente antineoplásicos na inibição da interação entre ácidos nucleicos e a proteína hnRNP K

Abstract

Cancer can be defined as a chronic multifactorial disease, characterized by abnormal growth of transformed cells. Changes in sundry genes called proto-oncogenes, results in the development of cancers called neoplasms. Chemotherapy is the most used method for neoplasms treatment. Uses chemical substances which interfere on growth process and transformed cells division, but they destroy both cancer cells as the healthy ones. The hnRNP K protein is known for their role in several processes such as gene expression, chromatin organization, translation of the mRNA, RNA splicing and stability, mainly by linking of KH domains to nucleotides. The inadequate activation of hnRNP K has direct relation with the genesis of some cancers. In this context, the aim of this study was to plan, synthesize and evaluate the anticancer activity of a series of N-acilidrazonas which have structural similarity with the compound 17, originally from virtual screening done by Silva in 2010, and can possibly establish interactions with the KH3 domain from protein hnRNP K. The antineoplastic activity was evaluated in vitro by assaying electrophoretic mobility shift (EMSA) for testing protein-DNA interactions in presence of the compounds. Among the 14 compounds synthesized and evaluated, only compound 5 have showed capability to bond to and inhibit KH3 hnRNP K protein being identified after analyzing the docking results, three possible modes of connection between the protein and compound.