Chalcone-thiosemicarbazone Hybrids as Inhibitors of Human Hepatocellular Carcinoma HepG2 Cells Viability and Oxygen Consumption

Abstract

Background: Chalcones are open-chain flavonoids especially attractive to medicinal chemistry due to their easy synthesis and the possibility of structural modifications. Objective: This study aims to evaluate the in vitro anticancer activity of a series of hybrids chalcones- thiosemicarbazones against the human hepatocellular carcinoma cell line HepG2. Methods: Seven hybrid chalcones-thiosemicarbazones (CTs), 3-(4’-X-phenyl)-1-phenylprop- 2-en-1-one thiosemicarbazone, where X=H (CT-H), CH3 (CT-CH3), NO2 (CT-NO2), Cl (CTCl), CN (CT-CN), F (CT-F), and Br (CT-Br), were synthesized and their effects on cells’ viability and mitochondrial oxygen consumption were assessed. Results: Incubation with CTs caused a decrease in HepG2 cells viability in a time-concentration-dependent manner. The most effective compounds in inhibiting cell viability, after 24 hours of treatment, were CT-Cl and CT-CH3 (IC50 20.9 and 23.63 μM, respectively). In addition, using 10 μM and only 1 hour of pre-incubation, CT-CH3 caused a reduction in basal respiration (-37 %), oxygen consumption coupled with ATP synthesis (-60 %), and maximum oxygen consumption (-54 %). These alterations in respiratory parameters may be involved with the inhibitory effects of CT-CH3 since significant changes in oxygen consumption rates were observed in a condition that anticipates more significant losses of cell viability. The ADME parameters and the no violation of Lipinski Rule of Five showed that all compounds are safe. Conclusion: These results may contribute to the knowledge about the effects of CTs on these cells and the development of new treatments against HCCs.