Skip to main content
SpringerLink
Log in

Synthesis and study of new 5-substituted 1-acetyl-4-phenyl-3-pyrrolin-2-ones as potential antitumor agents

  • Published:
Chemistry of Heterocyclic Compounds Aims and scope

The treatment of 1-acetyl-5-bromo-4-phenyl-3-pyrrolin-2-one with appropriate silver salts in benzene promotes the substitution of bromine with chloride, fluoride, nitrite, nitrate, and thiocyanate groups. Biological testing of the newly synthesized compounds resulted in the discovery of moderate indoleamine 2,3-dioxygenase and matrix metalloproteinase inhibiting properties for NO2 and SCN derivatives in combination with low antitumor effect in vivo. However, testing of the NO2 derivative in mice with transplanted 4T1 mammary and CT-26 mouse colon carcinomas led to a considerable decrease in tumor volume and lung metastases without undesirable toxic effects evidencing potent tumor supressing properties.

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

Figure 1.
Figure 2.
Figure 3.

Similar content being viewed by others

References

  1. (a) Zhuang, C.; Miao, Z.; Zhu, L.; Dong, G.; Guo, Z.; Wang, S.; Zhang, Y.; Wu, Y.; Yao, J.; Sheng, C.; Zhang, W. J. Med. Chem. 2012, 55, 9630. (b) Michel, P.; Matagne, A.; Lallemand, B.; Kendam, B.; Differding, E.; Talaga, P.; Pasau, P. AU Patent 2005203276; Chem. Abstr. 2001, 135, 195495. (c) Kumar, N.; Iskander, G. WO Patent WO2007085042; Chem. Abstr. 2007, 147, 235006.

  2. Gouliaev, A. H.; Monster, J. B.; Veso, M.; Senning, A. Org. Prep. Proced. Int. 1995, 27, 273.

    Article  CAS  Google Scholar 

  3. Miyazaki, H.; Ogiku, T.; Sai, H; Moritani, Y.; Ohtani, A.; Ohmizu, H. Chem. Pharm. Bull. 2009, 57, 979.

    Article  CAS  PubMed  Google Scholar 

  4. (a) Hidalgo, M.; Echardt, S. G. J. Natl. Cancer Inst. 2001, 93, 178. (b) Shi, Z.-G.; Li, J.-P.; Shi, L.-L.; Li, X. Recent Pat. Anti-Cancer Drug Discovery 2012, 7, 74.

  5. Prendergast, G. C.; Chang, M. Y.; Mandik-Nayak, L.; Metz, R.; Muller, A. J. Curr. Med. Chem. 2011, 18, 2257.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. (a) Zulfiqar, B.; Mahroo, A.; Nasir, K.; Farooq, R. K.; Jalal, N.; Rashid, M. U.; Asghar, K. OncoTargets Ther. 2017, 10, 463. (b) Di Pucchio, T.; Silvio, D.; De Cristofaro, R.; Rutella, S. Expert Opin. Ther. Pat. 2010, 20, 229.

  7. Uyttenhove, C.; Pilotte, L.; Theate, I.; Sroobant, V.; Colau, D.; Parmentier, N.; Boon, T.; Van den Ende, B. J. Nat. Med. 2003, 9, 1269.

    Article  CAS  PubMed  Google Scholar 

  8. (a) Katz, J. B.; Muller, A. J.; Prendergast, G. C. Immunol. Rev. 2008, 222, 206. (b) Muller, A. J.; Scherle, P. A. Nat. Rev. Cancer 2006, 6, 613.

  9. Vorona, M.; Orlova, N.; Kuznetsov, E.; Vikainis, S.; Liepinsh, E.; Belyakov, S.; Mishnev, A.; Veinberg, G. Chem. Heterocycl. Compd. 2013, 49, 1118. [Khim. Geterotsikl. Soedin. 2013, 1201.]

  10. Kornblum, N.; Hardies, D. E. J. Am. Chem. Soc. 1966, 88, 1707.

    Article  CAS  Google Scholar 

  11. (a) Liu, S.-C.; Yang, S.-F.; Yeh, K.-T.; Yeh, C.-M.; Chiou, H.-L.; Lee, C.-Y.; Chou, M.-C.; Hieh, Y.-S. Clin. Chim. Acta 2006, 371, 92. (b) Lv, F. Z.; Wang, J.-L; Wu, Y.; Chen, H.-F.; Shen X.-Y. Int. J. Immunopathol. Pharmacol. 2015, 28, 77.

  12. Ueda, J.; Kajita, M.; Suenaga, N.; Fujii, K.; Seiki, M. Oncogene 2003, 22, 8716.

    Article  CAS  PubMed  Google Scholar 

  13. Mackay, S.; Dong, W.; Edwards, C.; Henderson, A.; Gilmore, C. J.; Stewart, N.; Shankland, K.; Donald, A. maXus, Integrated Crystallography Software; Bruker-Nonius and University of Glasgow, 2003.

  14. Ponce, M. L. In Methods in Molecular Medicine. Angiogenesis Protocols, Murray, J. C., Ed.; Humana press, 2001, Vol. 46, p. 205.

  15. (a) Silk, J. D.; Lakhal, S.; Laynes, R.; Vallius, L.; Karydis, I.; Marcea, C.; Boyd, C. A. R.; Cerundolo, V. J. Immunol. 2011, 187, 1617. (b) Yue, E. W.; Douty, B.; Wayland, B.; Bower, M.; Liu, X.; Leffet, L.; Wang, G.; Bowman, K. J.; Hansbury, M. J.; Liu, C.; Wei, M.; Li, Y.; Wynn, R.; Burn, T. C.; Koblish, H. K.; Fridman, J. S.; Metcalf, B.; Sherle, P. A.; Combs, A. P. J. Med. Chem. 2009, 52, 7364.

  16. Mosmann, T. J. Immunol. Methods 1983, 65, 55.

    Article  CAS  PubMed  Google Scholar 

  17. Lewis, J. D.; Shearer, M. H.; Kennedy, R. C.; Bright, R. K. Cancer Res. 2005, 65, 2938.

    Article  CAS  PubMed  Google Scholar 

  18. National Institute for Environmental Health Sciences. ICCVAM. In Vitro Basal Cytotoxicity Test Methods for Estimating Acute Oral Systemic Toxicity. Research Triangle Park; http://iccvam.niehs.nih.gov/methods/acutetox/inv_nru_brd.htm.

Download references

This work was supported by The Latvian Council of Science (project No. 593/2014) and The National Research program: Biomedicine for Public Health No. 3 (2014-2017).

Author information

Authors and Affiliations

  1. Latvian Institute of Organic Synthesis, 21 Aizkraukles, Riga, LV-1006, Latvia

    Jevgenijs Kuznecovs, Maxim Vorona, Ilona Domraceva, Iveta Kanepe-Lapsa, Marina Petrova, Edvards Liepins, Sergey Belyakov & Grigory Veinberg

  2. Latvian Biomedical Research and Study Center, 1 Ratsupites, Riga, LV-1067, Latvia

    Ainars Leonchiks

Authors
  1. Jevgenijs Kuznecovs
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maxim Vorona
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ilona Domraceva
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Iveta Kanepe-Lapsa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marina Petrova
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Edvards Liepins
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sergey Belyakov
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ainars Leonchiks
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Grigory Veinberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Grigory Veinberg.

Additional information

Published in Khimiya Geterotsiklicheskikh Soedinenii, 2018, 54(5), 514–519

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kuznecovs, J., Vorona, M., Domraceva, I. et al. Synthesis and study of new 5-substituted 1-acetyl-4-phenyl-3-pyrrolin-2-ones as potential antitumor agents. Chem Heterocycl Comp 54, 514–519 (2018). https://doi.org/10.1007/s10593-018-2298-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10593-018-2298-7

Keywords

Search

Navigation