Vivian Cordeiro Rodrigues
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William Queiroz Felippe
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Carla Marins Goulart
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Aurea Echevarria
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Ana Paula Pereira da Silva
Background:
Chalcones are open-chain flavonoids especially attractive to medicinal chemistry due to their easy synthesis and the possibility of structural modifications.
Objective:
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 (CT-Cl), CN (CT-CN), F (CT-F) and Br (CT-Br), were synthesized and their effects on cells viability and mitochondrial oxygen consumption were accessed.
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 M 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.