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

Abstract

Cancer is a complex disease and a public health problem worldwide. Despite current advances in cancer therapy, many patients display unsatisfactory clinical responses to available drugs, which reinforces the continuous need for searching for new antitumor prototypes. Data from the literature have highlighted compounds containing acylhydrazone or benzyl-piperidine subunits for their significant antiproliferative activity on tumor cells. Herein, 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 an increased G2/M population in samples treated with 6i (at 60 µM) and a reduced frequency of cells in the 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.