Synthesis of new 4-azolidinones with 3,5-diaryl-4,5-dihydropyrazole moiety and evaluation of their antitumor activity in vitro

Authors

  • Dmytro Havrylyuk Danylo Halytskyi Lviv National Medical University, Department of Pharmaceutical, Organic and Bioorganic Chemistry, Ukraine Author
  • Nataliya Kovach Danylo Halytskyi Lviv National Medical University, Department of Pharmaceutical, Organic and Bioorganic Chemistry, Ukraine Author
  • Borys Zimenkovsky Danylo Halytskyi Lviv National Medical University, Department of Pharmaceutical, Organic and Bioorganic Chemistry, Ukraine Author
  • Roman Lesyk Danylo Halytskyi Lviv National Medical University, Department of Pharmaceutical, Organic and Bioorganic Chemistry, Ukraine Author

DOI:

https://doi.org/10.12923/

Keywords:

4-azolidinones, 3,5-diaryl-4,5-dihydropyrazoles, acylation, alkylation, 1H NMR spectra, antitumor activity

Abstract

In the present paper, a synthetic approach for design of new pyrazoline substituted 4-azolidones were described. Six of the synthesized compounds were tested according to NCI protocol and two of them (4d, 4e) displayed antitumor activity on leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate and breast cancers cell lines.

References

1. Abadi A.H. et al.: Synthesis of novel 1,3,4-trisubstituted pyrazole derivatives and their evaluation as antitumor and antiangiogenic agents. Chem. Pharm. Bull., 51, 838, 2003.

2. Beswick M.C. et al.: 3-(2-Hydroxy-phenyl)-1H-pyrazole-4-carboxylic acid amide derivatives as HSP90 inhibitors for the treatment of cancer. US 2007/0112192.

3. Carter P. H. et al.: Photochemically enhanced binding of small molecules to the tumor necrosis factor receptor-1 inhibits the binding of TNF-alpha. Proc. Natl. Acad. Sci. USA, 98, 11879, 2001.

4. Cutshall N. S. et al.: Rhodanine derivatives as inhibitors of JSP-1. Bioorg. Med. Chem. Lett., 15, 3374, 2005.

5. Dayam R. et al.: Discovery of small molecule integrin αvβ3 antagonists as novel anticancer agents. J. Med. Chem., 49, 4526, 2006.

6. Degterev A. et al.: Identification of small-molecule inhibitors of interaction between the BH3 domain and Bcl-xL. Nature Cell. Biol., 3, 173, 2001.

7. Havrylyuk D. et al.: Synthesis of novel thiazolone-based compounds containing pyrazoline moiety and evaluation of their anticancer activity. Eur. J. Med. Chem., 44, 1396, 2008.

8. http://dtp.nci.nih.gov

9. Kaminskyy D., Zimenkovsky B., Lesyk R.: Synthesis and in vitro anticancer activity of 2,4-azolidinedione-acetic acids derivatives. Eur. J. Med. Chem., 44, 3627, 2009.

10. Lin R. et al.: Design, synthesis, and evaluation of 3,4-disubstituted pyrazole analogues as anti-tumor CDK inhibitors. Bioorg. Med. Chem. Lett., 17, 4557, 2007.

11. Manna F. et al.: Synthesis of some pyrazole derivatives and preliminary investigation of their affinity binding to P-glycoprotein. Bioorg. Med. Chem. Lett., 15, 4632, 2005.

12. Palaska E. et al.: Synthesis and antidepressant activities of some 3,5-diphenyl-2-pyrazolines. Eur. J. Med. Chem., 36, 539, 2001.

13. Popov-Pergal К. et al.: Condensation of 2,4-dioxotetrahydro-1,3-thiazole with aromatic aldehydes. J. Gen. Chem. USSR, 61, 1958, 1991.

14. Shoemaker R. H.: The NCI60 human tumour cell line anticancer drug screen. Nature Rev. Cancer, 6, 813, 2006.

15. Zimenkovskii B.S. et al.: Synthesis and antimicrobial activity of 2,4-dioxothiazolidine-5-acetic acid amides. Pharm.Chem. J., 40, 303, 2006.

Downloads

Published

2010-09-30

Issue

Vol. 23 No. 3 (2010): Annales UMCS, Pharmacia, Sectio DDD, Volume XXIII

Section

Artykuły

License

Copyright (c) 2010 Authors

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 Unported License.