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Synthesis, Antitumor Activity Evaluation and Mechanistic Study of Novel Bis-Heterocyclic Chalcones Against Liver
Zhifen Li1, Jingbo Ma2, Xiannian Lv3
1School of Chemistry and Chemical Engineering, Shanxi Datong University, Datong, Shanxi, P. R. China.
Background:
Chalcones and heterocyclic compounds exhibit remarkably high activity in medicinal chemistry. In recent years, bis-chalcones have been reported to possess excellent anticancer activity. We synthesized a series of bis-heterocyclic chalcones via asymmetric chain synthesis, with the aim of making new discoveries in anticancer activity.
Methods:
Bis-heterocyclic chalcones were synthesized via Claisen-Schmidt condensation and alkylation reactions. The inhibitory activities of the synthesized compounds against Huh-1, Huh-7, and HepG2 cell lines were evaluated using the CCK-8 assay. Furthermore, the mechanism of action of these compounds was explored through live/dead cell staining, flow cytometric analysis, and Western blotting experiments.
Results:
Twelve bis-heterocyclic chalcone compounds were synthesized. All synthesized compounds were fully characterized by spectroscopic methods and evaluated for their cytotoxic activities against Huh-1, Huh-7, and HepG2 cell lines using the CCK-8 assay at concentrations ranging from 0 to 100 μM. Among them, derivative 3f exhibited the most potent cytotoxicity against Huh-7 (IC50 = 8.40 μM) and Huh-1 (IC50 = 6.75 μM), whereas HepG2 cells were most sensitive to compound 3d (IC50 = 27.99 μM). The mechanisms underlying the antitumor effects of 3d and 3f were further investigated through live/dead cell staining, flow cytometry, and western blot analysis. The results demonstrate that both compounds effectively induce apoptosis in liver cancer cells.
Conclusions:
Bis-heterocyclic chalcone compounds exhibit favorable inhibitory activity against hepatocellular carcinoma cells by inducing cell apoptosis, and thus can serve as a class of pharmaceutically active structural units for further in-depth research and screening.
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