Advertisement

Journal of Chemical Sciences

, Volume 125, Issue 5, pp 1029–1043 | Cite as

Design, synthesis and cytotoxic activity of some novel compounds containing pyrazolo[3,4-d]pyrimidines nucleus

  • MANAL M KANDEEL
  • SAMEHA M ROSHDY
  • EMAN K A ABDELALL
  • MOHAMED A ABDELGAWAD
  • PHOEBE F LAMIEEmail author
Article

Abstract

Novel pyrazolo[3,4-d]pyrimidines were designed and synthesized as antitumour agents against human breast cancer adenoma (MCF-7). Molecular modelling and pharmacological screening were performed against breast cancer cell line and also certain synthetic pathways were developed in order to introduce functionality onto C6 and N5 positions of pyrimidine moiety. Surprisingly, all the test compounds showed IC50 lower than that of the standard olomoucine I, especially compounds 4b, 8a, 10b, 11a and b, which showed IC50 between 0.009 and 0.004 \(\upmu \)M.

Graphical Abstract

Compounds with substitution on 1, 5 and 6 sites of pyrazolo [3,4-d] pyrimidinones were synthesized to match the action of cyclin-dependent kinases (CDK) inhibitors. The newly synthesized compounds were evaluated in vitro for their anticancer activity. There was some sort of consistency between modelling study and results of anticancer screening.

Keywords

Pyrazolo[3,4-d]pyrimidine derivatives cytotoxic activity MCF-7 cyclin-dependent kinase inhibitors (CDKI) 

References

  1. 1.
    Yenugonda V M, Deb T B, Grindrod S C, Dakshanamurthy S, Yang Y, Paige M and Brown M L 2011 Bioorg. Med. Chem. 19 2714Google Scholar
  2. 2.
    Otyepka M, Krystof V, Havlicek L, Siglerova V, Strnda M and Koca J 2000 J. Med. Chem. 43 2506CrossRefGoogle Scholar
  3. 3.
    Cavasotto C N, Ortiz M A, Abagyan R A and Piedrafita F J 2006 Bioorg. Med. Chem. Lett. 16 1969CrossRefGoogle Scholar
  4. 4.
    Peat A J, Garrido D, Boucheron J A, Schweiker S L, Dickerson S H, Wilson J R, Wang T Y and Thomson S A 2004 Bioorg. Med. Chem. Lett. 14 2127CrossRefGoogle Scholar
  5. 5.
    Peat A J, Boucheron J A, Dickerson S H, Garrido D, Mills W, Peckham J, Preugschat F, Smalley T, Schweiker S L, Wilson J R, Wang T Y, Zhou H Q and Thomson S A 2004 Bioorg. Med. Chem. Lett. 14 2121CrossRefGoogle Scholar
  6. 6.
    Gupta S, Rodrigues L M, Esteves A P, Oliveira-Campos A M F, Nascimento M S J, Nazareth N, Cidade H, Neves M P, Fernandes E, Pinto M, Cerqueira N M F S A and Bras N 2008 Eur. J. Med. Chem. 43 771CrossRefGoogle Scholar
  7. 7.
    Huang X, Finerty P Jr, walker J R, Butler-Cole C, Vedadi M, Schapira M, Parker S A, Turk B E, Thompson D A and Dhe-Paganon S 2009 J. Struct. Biol. 165 88Google Scholar
  8. 8.
    Schenone S, Zanoli S, Brullo C, Crespan E and Maga G 2008 Curr. Drug Therapy 3 158CrossRefGoogle Scholar
  9. 9.
    Huang H, Ma J, Shi J, Meng L, Jiang H, Ding J and Liu H 2010 Bioorg. Med. Chem. 18 4615CrossRefGoogle Scholar
  10. 10.
    Tintori C, Magnani M, Schenone S and Botta M 2009 Eur. J. Med. Chem. 44 990CrossRefGoogle Scholar
  11. 11.
    Kumar A, Ahmad I, Chhikara B S, Tiwari R, Mandal D and Parang K 2011 Bioorg. Med. Chem. Lett. 21 1342CrossRefGoogle Scholar
  12. 12.
    Baraldi P G, El-Kashef H, Farghaly A R, Vanelle P and Fruttarolo F 2004 Tetrahedron 60 5093CrossRefGoogle Scholar
  13. 13.
    Salaheldin A M, Oliveira-Campos A M F and Rodrigues L M 2009 Synth. Commun. 39 1186CrossRefGoogle Scholar
  14. 14.
    Park K S, Kim J, Chong Y and Choo H 2007 Bull. Korean Chem. Soc. 28 211CrossRefGoogle Scholar
  15. 15.
    Ibrahim D A, El-Metwally A M and Al-Arab E E 2009 Arkivoc vii 12Google Scholar
  16. 16.
    Patrick G L 2008 An introduction to medicinal chemistry 4th edn. (England: Oxford) p. 519Google Scholar
  17. 17.
    Abunada N M, Hassaneen H M, Kandile N G and Miqdad O A 2008 Molecules 13 1501CrossRefGoogle Scholar
  18. 18.
    Dave C G and Shah R D 2002 Molecules 7 554CrossRefGoogle Scholar
  19. 19.
    Ismail Z H, Abdel-Gawad S M, Abdel-Aziem A and Ghorab M M 2003 Phosphorus Sulfur Silicon 178 1795CrossRefGoogle Scholar
  20. 20.
    Rashad A E, Hegab M I, Abdel-Megeid R E, Fathalla N and Abdel-Megeid F M E 2009 Eur. J. Med. Chem. XXX 1Google Scholar
  21. 21.
    Rashad A E, Hegab M I, Abdel-Megeid R E, Micky J A and Abdel-Megeid F M E 2008 Bioorg. Med. Chem. 16 7102CrossRefGoogle Scholar
  22. 22.
    Schenone S, Bruno O, Bondavalli F, Ranise A, Mosti L, Menozzi G, Fossa P, Donnini S, Santoro A, Ziche M, Manetti F and Botta M 2004 Eur. J. Med. Chem. 39 939CrossRefGoogle Scholar
  23. 23.
    Moukha-Chafiq O and Taha M L 2006 Nucleos. Nucleot. Nucl. Acids 25 849CrossRefGoogle Scholar
  24. 24.
    Ghorab M M, Ragab F A, Alqasoumi S I, Alafeefy A M and Aboulmagd S A 2010 Eur. J. Med. Chem. 45 171CrossRefGoogle Scholar
  25. 25.
    Schenone S, Bruno O, Radi M and Botta M 2009 Mini-rev. Org. Chem. 6 220CrossRefGoogle Scholar
  26. 26.
  27. 27.
    Warren J, Bokesch H, Kenney S and Boyed M R 1990 J. Nat. Cancer Inst. 82 1107CrossRefGoogle Scholar
  28. 28.
    Marsico J et al. 1973 United States Patent, 3,760,084, 18 SeptemberGoogle Scholar

Copyright information

© Indian Academy of Sciences 2013

Authors and Affiliations

  • MANAL M KANDEEL
    • 1
  • SAMEHA M ROSHDY
    • 1
  • EMAN K A ABDELALL
    • 2
  • MOHAMED A ABDELGAWAD
    • 2
  • PHOEBE F LAMIE
    • 2
    Email author
  1. 1.Pharmaceutical Organic Chemistry Department, Faculty of PharmacyCairo UniversityGizaEgypt
  2. 2.Pharmaceutical Organic Chemistry Department, Faculty of PharmacyBeni Suef UniversityBeni SuefEgypt

Personalised recommendations