PQM-75: A N-benzyl-piperidine Acyl-hydrazone Derivative with Inhibitory Effects on Clonogenic Capacity and Cell Cycle Progression of HepG2 Cells

Resumo

Cancer is a complex disease and a public health problem worldwide. Despite current advances in cancer therapy, many patients display unsatisfactory clinical response to available drugs, which reinforce the continuous need for searching new antitumor prototypes. Data from literature have highlighted compounds containing acylhydrazone or benzyl-piperidine subunits for their significant antiproliferative activity on tumor cells. Here in, we report the evaluation of a series of N-benzyl-piperidinyl acylhydrazone hybrid derivatives (6a-k) for their cytotoxic profiles on A549 (non-small cell lung cancer) and HepG2 (hepatocellular carcinoma). As a result, derivatives PQM-75 (6i, (IC₅₀= 58.40 ± 1.87 µM) and PQM-88 (6k, IC₅₀= 59.58 ± 4.07 µM) showed the best antiproliferative activities against HepG2 and A549 cell lines, respectively. In addition, we demonstrated that compound 6i drastically reduced the clonogenic capacity of HepG2 cell cultures in comparison to control groups. We also observed increased G2/M population in samples treated with 6i (at 60 µM) and reduced frequency of cells in S-phase. In addition, the frequency of cells in mitosis was higher in treated samples compared to control groups. In a conclusion, derivative PQM-75 (6i) displays antiproliferative activity on HepG2 cells due to its ability to promote M-phase arrest.