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

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

Volume: 18 Issue: 9

Author(s): Vivian Cordeiro Rodrigues, William Queiroz Felippe, Carla Marins Goulart, Aurea Echevarria and Ana Paula Pereira da Silva*

Affiliation:

• Department of Biochemistry, Federal Rural University of Rio de Janeiro, Seropédica, Rio de Janeiro, Brazil

Keywords: Liver cancer, chalcone, thiosemicarbazone, hybrid compounds, anticancer agents, mitochondria, 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.

Cite this article as:

Rodrigues Cordeiro Vivian, Felippe Queiroz William, Goulart Marins Carla, Echevarria Aurea and da Silva Paula Pereira Ana*, Chalcone-thiosemicarbazone Hybrids as Inhibitors of Human Hepatocellular Carcinoma HepG2 Cells Viability and Oxygen Consumption, Current Bioactive Compounds 2022; 18 (9) : e110122200130 . https://dx.doi.org/10.2174/1573407218666220111104011