Investigação da atividade antiproliferativa de derivados N-Benzil-piperidínicos acilidrazônicos

Abstract

The incidence of cancer is increasing because of the growth and aging of the population as well as risks factors such as smoking, sedentary lifestyle and obesity. Mortality rate is elevated in both more-developed and less-developed countries. Data from the INCA, it is estimated in 2016- 2017 around 600 thousand new cases of cancer in Brazil, with female breast cancer and prostate cancer being the most frequent. Several challenges should be overcome to improve the cancer treatment such as improving the drug efficiency and selectivity, reducing toxicity and tumor resistance mechanism. In addition, the cost of medicines is expensive for population. Thus, the present work aims to evaluate the antiproliferative activity of a series of N-benzyl piperidinyl acylhydrazone derivatives. In a preliminary screening eleven substances were tested against four human tumor cell lines (MCF7, HT144, A549, HepG2). According to results, PQM-66 (32f), PQM-67 (32g), PQM- 76 (32j), and PQM-88 (32k) reduced significantly the viability of A549 cells with IC50 de 139.20 μM; 116.60 μM; 120.50 μM and 53.92 μM, respectively. Interestingly, PQM-75 (32i) showed more promising activity against the other 3 lineages (MCF-7, HepG2 e HT144). Thus, compound 32i was selected for evaluation of its antiproliferative potential on HepG2 cells. Data showed that 32i reduced 60% and 70% clonogenic capacity of HepG2 with treated 30 μM and 60 μM, respectively and induced cell cycle arrest. Therefore, the reduction in cell viability, initially observed through MTS assay, is associated to ability of 32i in inhibiting the proliferation of HepG2 cells. Additional studies should be performed to investigate the influence of compound 32i on expression profile of regulators of cell cycle.