Skip to main content
SpringerLink
Log in

Synthesis and evaluation of cytotoxicity of 6-amino-4-aryl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitriles

  • Published:
Russian Journal of Bioorganic Chemistry Aims and scope Submit manuscript

Abstract

Several derivatives of 6-amino-4-aryl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitriles were synthesized via Biginelli type reaction and tested for their anti-proliferative activity on human breast cancer (MCF-7) and human colon carcinoma (HT29) cell lines. Malignant and non-malignant cells were cultivated in RPMI medium and incubated with different concentrations of these pyrimidines. Cell viability was evaluated by MTT assay. Apoptotic cells were determined using DAPI (4'-6-diamidino-2-phenylindole) and propidium iodide staining of DNA fragmentation by flow cytometry (sub-G1 peak). 6-Amino-4-(4-chlorophenyl)-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile and 6-amino-4-[4-dimethylamino)phenyl]-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile decreased the viability of MCF-7 and HT29 cells, in contrast to L929 cells. These compounds induced a sub-G1 peak inflow cytometry histograms of treated cells indicating that apoptosis is involved in their toxicity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. The International Agency for Research on Cancer (IARC) Latest World Cancer Statistics, 2013, December 12. http://www.iarc.fr/en/media-centre/pr/2013/ pdfs/pr223_E.pdf

  2. Goldstein, C.M., Mehren, M.V., Gradel, T., Kilpatrick, D., Vaders, L., Brady, D., and Vogel, L., Breast Cancer Research, Fox Chase Cancer Center Scientific Report, Philadelphia, 2000.

    Google Scholar 

  3. Parkin, D.M., Bray, F., Ferlay, J., and Pisani, P., CA Cancer. J. Clin., 2005, vol. 55, pp. 74–108.

    Article  PubMed  Google Scholar 

  4. Eidinoff, M.L., Knoll, J.E., Marano, B.J., and Klein, D., Cancer. Res., 1961, vol. 21, pp. 1377–1385.

    CAS  PubMed  Google Scholar 

  5. Callery, P., and Gannett, P., in Cancer and Cancer Therapy, William, D.A. and Lemke, T.L., Eds., Phila delphia, PA, USA: Lippincot Williams and Wilkins, 2002, pp. 934–935.

  6. Donnini, S., Monti, M., Castagnini, C., Solito, R., Botta, M., Schenone, S., Giachetti, A., and Ziche, M., Int. J. Cancer, 2006, vol. 120, pp. 995–1004.

    Article  Google Scholar 

  7. Bazgir, A., Khanaposhtani, M. M., and Soorki, A.A., Bioorg. Med. Chem., 2008, vol. 18, pp. 5800–5803.

    Article  CAS  Google Scholar 

  8. Shaban, N.Z., Masoud, M.S., Mawlawi, M.A., Awad, D., and Sadek, O.M., J. Physiol. Biochem., 2012, vol. 68, pp. 475–484.

    Article  CAS  PubMed  Google Scholar 

  9. Sawyer, R.C., Stolfi, R.L., Martin, D.S., and Balis, M.E., Biochem. Pharmacol., 1989, vol. 38, pp. 2305–2311.

    Article  CAS  PubMed  Google Scholar 

  10. Ghoshal, K., and Jacob, S.T., Biochem. Pharmacol., 1997, vol. 53, pp. 1569–1575.

    Article  CAS  PubMed  Google Scholar 

  11. Yang, S., Li, Z., Jin, L., Song, B., Liu, G., Chen, J., Chen, Z., Hu, D., Xue, W., and Xu, R., Bioorg. Med. Chem. Lett., 2007, vol. 17, pp. 2193–2196.

    Article  CAS  PubMed  Google Scholar 

  12. Prachayasittikul, S., Worachartcheewan, A., Nantasenamat, C., Chinworrungsee, M., Sornsongkhram, N., Ruchirawat, S., and Prachayasittikul, V., Eur. J. Med. Chem., 2011, vol. 46, pp. 738–742.

    Article  CAS  PubMed  Google Scholar 

  13. Sharma, S.K., Kumar, P., Narasimhan, B., Ramasamy, K., Mani, V., Mishra, R.K., and Majeed, A.B., Eur. J. Med. Chem., 2012, vol. 48, pp. 16–25.

    Article  CAS  PubMed  Google Scholar 

  14. Taher, A.T. and Helwa, A.A., Chem. Pharm. Bull., 2012, vol. 60, pp. 521–530.

    Article  CAS  PubMed  Google Scholar 

  15. Taher, A.T. and Abou-Seri, S.M., Molecules, 2012, vol. 17, pp. 9868–9886.

    Article  CAS  PubMed  Google Scholar 

  16. Fargualy, A.M., Habib, N.S., Ismail, K.A., Hassan, A.M., and Sarg, M.T., Eur. J. Med. Chem., 2013, vol. 66, pp. 276–295.

    Article  CAS  PubMed  Google Scholar 

  17. Ghodasara, H.B., Trivedi, A.R., Kataria, V.B., Patel, B.G., and Shah, V.H., Med. Chem. Res., 2013, vol. 22, pp. 6121–6128.

    Article  CAS  Google Scholar 

  18. Prachayasittikul, S., Sornsongkhram, N., Pingarew, R., Techatanachai, S., Ruchirawat, S., and Prachayasittikul, V., Eur. J. Sci. Res., 2009, vol. 36, pp. 236–245.

    Google Scholar 

  19. Tozkoparan, B., Yarim, M., Saraç, S., Ertan, M., Kelicen, P., Altinok, G., and Demirdamar, R., Arch. der Pharmazie, 2000, vol. 333, pp. 415–420.

    Article  CAS  Google Scholar 

  20. Bakavoli, M., Rahimizadeh, M., Shiri, A., Akbarzadeh, M., Mousavi, S. H., Atapour-Mashhad, H., and Tayarani-Najaran, Z., J. Chem. Res., 2010, pp. 403–406.

    Google Scholar 

  21. Bakavoli, M., Rahimizadeh, M., Shiri, A., Akbarzadeh, M., Mousavi, S. H., Tayarani-Najaran, Z., Atapour-Mashhad, H., and Nikpour, M., J. Het. Chem., 2011, vol. 48, pp. 183–187.

    Article  CAS  Google Scholar 

  22. Pisani, P., Parkin, D.M., and Ferlay, J., Int. J. Cancer, 1993, vol. 55, pp. 891–903.

    Article  CAS  PubMed  Google Scholar 

  23. Fogh, J., Fogh, J.M., and Orfeo, T., J. Natl. Cancer. Inst., 1977, vol. 59, pp. 221–226.

    CAS  PubMed  Google Scholar 

  24. Navio, J.L.G., Lorente, A., and Soto, J.L., Heterocycles, 1982, vol. 19, pp. 305–311.

    Article  Google Scholar 

  25. Fadda, A.A., El-Latif, E.A., Bondock, S., and Samir, A., Synth. Commun., 2008, vol. 38, pp. 4352–4368.

    Article  CAS  Google Scholar 

  26. Jung, M.H., Kim, H., Choi, W.K., El-Gamal, M.I., Park, J.H., Yoo, K.H., Sim, T.B., Lee, S.H., Baek, D., Hah, J.M., Cho, J.H., and Oh, C.H., Bioorg. Med. Chem. Lett., 2009, vol. 19, pp. 6538–6543.

    Article  CAS  PubMed  Google Scholar 

  27. Zhao, L., Chen, Z., Wang, J., Yang, L., Zhao, Q., Wang, J., Qi, Q., Mu, R., You, Q.D., and Guo, QL., Cancer. Chemother. Pharmacol., 2009, vol. 10, pp. 1053–1052.

    Google Scholar 

  28. Yu, B., Shi, X.J., Zheng, Y.F., Fang, Y., Zhang, E., Yu, D.Q., and Liu, H.M., Eur. J. Med. Chem., 2013, vol. 69, pp. 323–330.

    Article  CAS  PubMed  Google Scholar 

  29. Kemnitzer, W., Sirisoma, N., May, C., Tseng, B., Drewe, J., and Cai, S.X., Bioorg. Med. Chem. Lett., 2009, vol. 1, pp. 3536–3540.

    Article  Google Scholar 

  30. Atapour-Mashhad, H., Tayarani-Najaran, Z., Davoodnia, A., Moloudi, R., and Mousavi, S. H., Drug. Chem. Toxicol., 2011, vol. 34, pp. 271–276.

    Article  CAS  PubMed  Google Scholar 

  31. Mousavi, S.H., Tayarani-Najaran, Z., and Hersey, P., Iran. J. Basic. Med. Sci., 2008, vol. 11, pp. 121–142.

    CAS  Google Scholar 

  32. Brohem, C.A., Sawada, T.C., Massaro, R.R., Almeida, R.L., Rivelli, D.P., Ropke, C.D., da Silva, V.V., de Lima, T.M., Curi, R., Barros, S.B., and Maria-Engler, S.S., Toxicol. In Vitro, 2009, vol. 23, pp. 111–119.

    Article  CAS  PubMed  Google Scholar 

  33. Mosmann, T., J. Immunol. Meth., 1983, vol. 65, pp. 55–63.

    Article  CAS  Google Scholar 

  34. Mousavi, S. H., Tavakkol-Afshari, J., Brook, A., and Jafari-Anarkooli, I., Food. Chem. Toxicol., 2009, vol. 47, pp. 1909–1913.

    Article  CAS  PubMed  Google Scholar 

  35. Mousavi, S.H., Atapour-Mashhad, H., Bakavoli, M., Shiri, A., Akbarzadeh, M., and Tayarani-Najaran, Z., Russ. J. Bioorg. Chem., 2015, vol. 41, pp. 201–208.

    Article  CAS  Google Scholar 

  36. Mousavi, S.H., Tavakkol-Afshari, J., Brook, A., and Jafari-Anarkooli, I., Food. Chem. Toxicol., 2009, vol. 47, pp. 855–859.

    Article  CAS  PubMed  Google Scholar 

  37. Tayarani-Najaran, Z., Mousavi, S.H., Asili, J., and Emami, S.A., Food. Chem. Toxicol., 2010, vol. 48, pp. 599–604.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Chemistry Department, Payame Noor University, 19395-4697, Tehran, I. R. Iran

    Hoda Atapour-Mashhad & Abdolhossien Massoudi

  2. Department of Clinical Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Mohammad Soukhtanloo

  3. Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, 91775-1436, Iran

    Ali Shiri & Mehdi Bakavoli

Authors
  1. Hoda Atapour-Mashhad
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohammad Soukhtanloo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Abdolhossien Massoudi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ali Shiri
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mehdi Bakavoli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mehdi Bakavoli.

Additional information

The article is published in the original.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Atapour-Mashhad, H., Soukhtanloo, M., Massoudi, A. et al. Synthesis and evaluation of cytotoxicity of 6-amino-4-aryl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitriles. Russ J Bioorg Chem 42, 316–322 (2016). https://doi.org/10.1134/S1068162016020047

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1068162016020047

Keywords

Search

Navigation