Amidas sintéticas derivadas do ácido ferúlico e avaliação da atividade citotóxica em células tumorais

Abstract

Cancer is one of the leading causes of death worldwide. Currently, 8.2 million people die each year from cancer worldwide (INCA, 2015). Amides derived from ferulic acid have a broad spectrum of pharmacological activities, including antitumor activity. The objective of this work was to evaluate the cytotoxic activity of ten amides derived from ferulic acid in four cell types, HepG2 (human hepatocellular carcinoma), HCT116 (human colon carcinoma), HL-60 (human promyelocytic leukemia) and MRC5 (Human fibroblast of the lung). These amides were prepared by coupling reactions using two types of coupling agents: benzotriazol-1-yloxy-tris- (dimethylamino) -phosphonium hexafluorophosphate (BOP) and dicyclohexylcarbodiimide (DCC) with 4-dimethylaminopyridine (DMAP). In the characterization of the products were used Infrared Spectroscopic Methods, 1H and 13C Nuclear Magnetic Resonance, as well as High Resolution Mass Spectrometry for the unpublished derivatives. All amides were submitted to cytotoxic tests using the blue alamar method, with doxorubicin as a positive control. The ten amides were obtained with yields varying between 43- 91 %, two of which were not published in the literature. Eight amides showed cytotoxic activity; however, two presented cytotoxicity to human fibroblast cells. The amines MA3, MA4, MA6, MA8, MA9 and MA10 were selective for the HL60 cell type (promyelocytic leukocyte cells). MA9 showed the lowest IC50. The results show that compounds with substituents containing two methoxy groups at the meta and para positions of the benzyl ring have an increase in cytotoxic activity, of the benzyl ring have an increase in cytotoxic activity, and selectivity for the HL60 tumor cell type.