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Anti-liver and anti-breast cancer activities of 2-thioxo-4-imidazolidinone derivatives

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Abstract

MTT assay and flow cytometry analysis were used to examine the anti-liver (HepG2) and anti-breast cancer (MCF-7) activities of twelve compounds derived from 2-thioxo-4-imidazolidine. The compounds 5a–h and 7g demonstrated significant anticancer activity against breast cancer cells, while the compounds 5a, 5b, and 5d–h demonstrated significant anticancer activity against liver cancer cells, with varying IC50 values as compared to Cisplatin as the positive control. Among these compounds, we chose 5a, 5d, and 5h to detect cell-cycle phases and late apoptosis. Compound 5a arrested MCF-7 cells in the S phase, while compound 5d arrested cells in the G1 phase. Compound 5a arrested S phase HepG2 cells, compound 5d arrested S phase cells, and compound 5h arrested G2 phase HepG2 cells. Compound 5a had a higher ratio of late apoptosis than compounds 5d and 5h on both cancer cells. Finally, further research will be conducted to develop these compounds as new anti-breast and anti-liver agents.

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References

  1. Ma R, Feng Y, Lin S, Chen J, Lin H, Liang X, et al. Mechanisms involved in breast cancer liver metastasis. J Transl Med. 2015;13:64. https://doi.org/10.1186/s12967-015-0425-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Bai G, Wang Y, Zhu Y, Guo L. Prediction of early response to chemotherapy in breast cancer liver metastases by diffusion-weighted MR imaging. Technol Cancer Res Treat. 2019;18:1533033819842944. https://doi.org/10.1177/1533033819842944.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Martins P, Jesus J, Santos S, Raposo LR, Roma-Rodrigues C, Baptista PV, et al. Heterocyclic anticancer compounds: recent advances and the paradigm shift towards the use of nanomedicine’s tool box. Molecules 2015;20:16852–91. https://doi.org/10.3390/molecules200916852.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Liu JC, Narva S, Zhou K, Zhang W. A review on the antitumor activity of various nitrogenous-based heterocyclic compounds as NSCLC inhibitors. Mini Rev Med Chem. 2019;19:1517–30. https://doi.org/10.2174/1389557519666190312152358.

    Article  CAS  PubMed  Google Scholar 

  5. Vengurlekar S, Sharma R, Trivedi P. A study on the biological activity of 2-thioxo-imidazolidin-4-ones. Lett Drug Des Discov. 2012;9:549–55.

    Article  CAS  Google Scholar 

  6. Colacino E, Lamaty F, Martinez J, Parrot, I. Microwave-assisted solid-phase synthesis of hydantoin derivatives. Tetrahedron Lett. 2007;48:5317.

    Article  CAS  Google Scholar 

  7. Klason P. An apparatus for preparing chloride. P Chem Ztg. 1890;14:543.

    Google Scholar 

  8. Karali N, Gursoy A, Terzioglu N, Ozkirimli S, Ozer H, Ekinci AC. Synthesis and preliminary CNS depressant activity evaluation of new 3-[(3-substituted-5-methyl-4-thiazolidinon-2-ylidene)hydrazono]-1H-2- indolinones and 3-[(2-thioxo-3-substituted-4,5-imidazolidinedion-1-yl)imino]-1H-2-indolinones. Arch Pharama Med Chem. 1998;331:254–8.

    Article  CAS  Google Scholar 

  9. Pelenope MM, Oscar L, Eleuterio A, José GFB. Synthesis of conformationally constrained thio (seleno) hydantoins and a-triazolyl lactones from D-arabinose as potential glycosidase inhibitors. Tetrahedron. 2012;68:4888–98.

    Article  Google Scholar 

  10. Thanusu J, Kanagarajan V, Gopalakrishnan M. Synthesis, spectral analysis and in vitro microbiological evaluation of 3-(3-alkyl-2,6-diarylpiperin-4-ylidene)-2-thioxoimidazolidin-4-ones as a new class of antibacterial and antifungal agents. BioorgMed Chem Lett. 2010;20:713–7.

    Article  CAS  Google Scholar 

  11. Puszyńska-Tuszkanow M, Grabowski T, Daszkiewicz M, Wietrzyk J, Filip B, Maciejewska G, et al. Silver (I) complexes with hydantoins and allantoin. J Inorg Biochem. 2011;105:17–22.

    Article  Google Scholar 

  12. Elhady HA, El-Sayed R, Al-Nathali HS. Design, synthesis and evaluation of anticancer activity of novel 2-thioxoimidazolidin-4-one derivatives bearing pyrazole, triazole and benzoxazole moieties. Chem Cent J. 2018;12:51. https://doi.org/10.1186/s13065-018-0418-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Finko AV, Skvortsov DA, Laikov DN, Averochkin GM, Dlin EA, Kalinina MA, et al. Synthesis and biological activity of 5-aryliden-2-thiohydantoin S-aryl derivatives. Bioorg Chem. 2020;100:103900. https://doi.org/10.1016/j.bioorg.2020.103900.

    Article  CAS  PubMed  Google Scholar 

  14. Ashraf AM, Abdullah NA, Surendra KR, Asser M, Akbar I. Biological evaluation of some imidazolidine-2,4-dione and 2-thioxoimidazolidin-4-one derivatives as anticoagulant agents and inhibition of MCF-7 breast cancer cell line. Int J Pharmacol. 2016;12:290–303.

    Article  Google Scholar 

  15. Oleh VS, Yurii EK, Victoriya VD, Olga VS, Volodymyr SB. Synthesis and anticancer activity of new substituted imidazolidinone sulfonamides. Curr Chem Lett. 2019;8:199–210.

    Google Scholar 

  16. Lafayette EA, de Almeida V, Sinara M, Da Rocha P, Marina G. Carneiro Beltrão, et al. Synthesis, DNA binding and topoisomerase I inhibition activity of thiazacridine and imidaz acridine derivatives. Molecules. 2013;18:15035–50. https://doi.org/10.3390/molecules181215035.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. AbdulJabar L, Mutalq D, Al-Shawi A. Synthesis of novel 2-thioxo-4-imidazolidinone derivatives and evaluation of their antibacterial, and antifungal activities. Egypt J Chem. 2021. https://doi.org/10.21608/ejchem.2021.66960.3442.

  18. Mohammed MK, Al-Shuhaib Z, Al-Shawi A. Synthesis, characterization and cytotoxicity appraisal of original 1, 2, 3-Triazole derivatives, against breast cancer cell lines (MDA-MB-231). Mediterr J Chem. 2019;9:305–10.

    Article  CAS  Google Scholar 

  19. Al-Shawi A, Hameed M, Ali NH, Hussein KA. Investigations of phytoconstituents, antioxidant and anti-liver cancer activities of Saueda monoica Forssk extracted by microwave-assisted extraction. Asian Pac J Cancer Prev. 2020;21:2349–55. https://doi.org/10.31557/APJCP.2020.21.8.2349.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Mossa GD, Al-Shawi A. Induction of apoptosis through S-phase in human breast cancer MDA-MB231 cells by ethanolic extract of dodonaea viscose L.-an Iraqi medicine plant. J Basrah Researches (Sci). 2015;41:1.

    Google Scholar 

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Acknowledgements

As part of the PhD graduation requirements, the Ministry of Higher Education and Scientific Researches has funded this research project at the University of Basrah College of Education for Pure Science in Iraq. The authors would like to thank the Central Instrument Laboratory at the University of Tehran for performing the 1H- and 13C-NMR, FT-IR, mass spectra, and flow cytometry experiments. The authors would also like to thank Dr Ali Abdullateef, Biology Department, College of Education for Pure Science, University of Basrah, Iraq, for his assistance with the MTT assay.

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Correspondence to Ali A. A. Al-Shawi.

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AbdulJabar, L.A., Al-Shawi, A.A.A. & Mutlaq, D.Z. Anti-liver and anti-breast cancer activities of 2-thioxo-4-imidazolidinone derivatives. Med Chem Res 30, 1943–1953 (2021). https://doi.org/10.1007/s00044-021-02769-8

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