A novel chromonyl thiohydantoin with anti-proliferative action on primary hepatocellular carcinoma cells

Abstract

Chromone, imidazolidinedione, thiohydantoin and 2,4-thiazolidinedione structures are known to be cytotoxic to cancer cells. In this study, biological activities of previously synthesized 18 chromonyl-2,4-thiazolidinediones/imidazolidinediones/thiohydantoins were tested by sulforhodamine B assay in five liver and one breast cancer cell lines. It was shown that a hybrid chromonyl thiohydantoin derivative C9 was able to significantly suppress the proliferation of the liver cancer cell lines which are very resistant to anticancer drugs. According to 50% growth inhibition concentrations of C9, well differentiated hepatocellular carcinoma cell line Huh7 and breast adenocarcinoma cell line Mcf7 cells are found to be highly sensitive to C9 with IC50 values between 4.9–5.2 µM. Poorly differentiated human liver cancer cell line Snu449 is found to be the most resistant to C9. Further studies show that C9 causes morphological changes in Snu449 cells. However, it does not induce significant senescence response or cell cycle arrest. On the other hand, Huh7 cells are found to be arrested in G2/M phase of the cell cycle after 24 and 72 h treatment. In conclusion, a novel chromonyl thiohydantoin hybrid molecule effectively stops or slows down the proliferation of well-differentiated hepatocellular carcinoma cells that exist in primary tumors.

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Acknowledgements

This work was supported by Research Organization of Ankara University, Turkey (No: 09B3336003 and 12B3336003). One of the authors was supported by TUBA DSAP program. Biological part of the study was supported by the Scientific and Technological Research Council of Turkey with project 113S389.

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Correspondence to Oya Bozdag-Dundar.

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Ozen, C., Ceylan-Unlusoy, M., Ozturk, M. et al. A novel chromonyl thiohydantoin with anti-proliferative action on primary hepatocellular carcinoma cells. Med Chem Res 27, 153–160 (2018). https://doi.org/10.1007/s00044-017-2037-0

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Keywords

  • Antiproliferative
  • Hepatocellular carcinoma
  • Liver cancer
  • Chromonyl-2,4-thiazolidinediones
  • Imidazolidinedione
  • Thiohydantoin