Medicinal Chemistry Research

, Volume 21, Issue 7, pp 1376–1383 | Cite as

Synthesis of novel pyrazole and pyrimidine derivatives bearing sulfonamide moiety as antitumor and radiosensitizing agents

  • Mostafa M. Ghorab
  • Fatma A. Ragab
  • Helmy I. Heiba
  • Hanan A. Youssef
  • Marwa G. El-Gazzar
Original Research
First Online:
Received:
Accepted:

Abstract

Several novel pyrazole 10–16 and pyrimidine 17–19 derivatives bearing Sulfonamide moieties were synthesized in order to study their antitumor activity. The synthesized compounds were characterized by elemental analysis, IR, 1H-NMR, and mass spectral data, then screened as antitumor agents against human tumor liver and breast cell lines (HEPG2 and MCF7). All the tested compounds were more potent than the reference drug doxorubicin on human liver (HEPG2) cell line, while on human breast cancer (MCF7) cell line, they were less potent than the reference drug. Additionally, some of the synthesized compounds were evaluated for their ability to enhance the cell killing effect of γ-radiation.

Keywords

Pyrazole Pyrimidine Sulfonamide Antitumor activity Radiation 
This is a preview of subscription content, log in to check access.

References

  1. Abou El Ella DA, Ghorab MM, Noaman E, Heiba HI, Khalil AI (2008) Molecular modeling study and synthesis of novel pyrrolo[2,3-d]pyrimidines and pyrrolotriazolopyrimidines of expected antitumor and radioprotective activities. Bioorg Med Chem 16:2391–2402PubMedCrossRefGoogle Scholar
  2. Anjaneyulu R, Anjaneyulu K, Couturier E, Malaisse WJ (1980) Opposite effects of hypoglycemic and hyperglycemic sulfonamides upon ionophore-mediated calcium transport. Biochem Pharm 29(13):1879–1882PubMedCrossRefGoogle Scholar
  3. Azas N, Rathelot P, Djekou S, Delmas F, Gellis A, Di Giorgio C, Vanelle P, Timon-David P (2003) Antiparasitic activity of highly conjugated pyrimidine-2,4-dione derivatives. Il Farmaco 58:1263–1270PubMedCrossRefGoogle Scholar
  4. Deshmukh MB, Salunkhe SM, Patil DR, Anbhule PV (2009) A novel and efficient one step synthesis of 2-amino-5-cyano-6-hydroxy-4-aryl pyrimidines and their anti-bacterial activity. Eur J Med Chem 44(6):2651–2654PubMedCrossRefGoogle Scholar
  5. Ezabadi IR, Camoutsis C, Zoumpoulakis P, Geronikaki A, Soković M, Glamočilija J, Ćirić A (2008) Sulfonamide-1,2,4-triazole derivatives as antifungal and antibacterial agents: synthesis, biological evaluation, lipophilicity, and conformational studies. Bioorg Med Chem 16(3):1150–1161PubMedCrossRefGoogle Scholar
  6. Geng C, Zeng Z, Wang J, Xuan S, Lin C (2005) Docetaxel shows radiosensitization in human hepatocellular carcinoma cells. World J Gastroenterol 11(19):2990–2993PubMedGoogle Scholar
  7. Gholap AR, Toti KS, Shrazi F, Deshpande MV, Srinivasan KV (2008) Efficient synthesis of antifungal pyrimidines via palladium catalyzed Suzuki/Sonogashira cross-coupling reaction from Biginelli 3, 4-dihydropyrimidin-2(1H)-ones. Tetrahedron 64(44):10214–10223CrossRefGoogle Scholar
  8. Ghorab MM, Ismail ZH, Abdel-Gawad SM, Abdel-Aziem A (2004) Antimicrobial activity of amino acid, imidazole and sulfonamide derivatives of pyrazolo[3,4-d]pyrimidine. Heteroatom Chem 15(1):57–62CrossRefGoogle Scholar
  9. Ghorab MM, Noaman E, Ismail MMF, Heiba HI, Ammar YA, Sayed MY (2006) Arzneimittelforschung 56(6):405–413PubMedGoogle Scholar
  10. Ghorab MM, Ragab FA, Noaman E, Heiba HI, El-Hossary E (2007) Synthesis of some novel quinolines and pyrimido [4,5-b] quinolines bearing A sulfonamide moiety as potential anticancer and radioprotective agents. Arzneimittelforschung 57(12):795–803PubMedGoogle Scholar
  11. Ghorab MM, Ragab FA, Hamed MM (2009) Design, synthesis and anticancer evaluation of novel tetrahydroquinoline derivatives containing sulfonamide moiety. Eur J Med Chem 44:4211–4217PubMedCrossRefGoogle Scholar
  12. Gokhan KN, Yabanoglu S, Kupeli E, Salgin U, Ozgen O, Ucar G, Yesilada E, Kendi E, Yesilada A, Bilgin AA (2007) A new therapeutic approach in Alzheimer disease: some novel pyrazole derivatives as dual MAO-B inhibitors and anti-inflammatory analgesics. Bioorg Med Chem 15(17):5775–5786CrossRefGoogle Scholar
  13. Ismail MMF, Ghorab MM, Noaman E, Ammar YA, Heiba HI, Sayed MY (2006) Novel synthesis of pyrrolo[2,3-d]pyrimidine bearing sulfonamide moieties as potential antitumor and radioprotective agents. Arzneimittelforschung 56(4):301–308PubMedGoogle Scholar
  14. Jaiswal M, Khadikar PV, Supuran CT (2004) Topological modeling of lipophilicity, diuretic activity, and carbonic inhibition activity of benzene sulfonamides: a molecular connectivity approach. Bioorg Med Chem Lett 14(22):5661–5666PubMedCrossRefGoogle Scholar
  15. Lin R, Chiu G, Yu Y, Connolly PJ, Li S, Lu Y, Adams M, Fuentes-Pesquera AR, Greenberger SLE (2007) Design, synthesis, and evaluation of 3,4-disubstituted pyrazole analogues as anti-tumor CDK inhibitors. Bioorg Med Chem Lett 17:4557–4561PubMedCrossRefGoogle Scholar
  16. Mitchell RE, Greenwood DR, Sarojini V (2008) An antibacterial pyrazole derivative from Burkholderia glumae, a bacterial pathogen of rice. Phytochemistry 69(15):2704–2707PubMedCrossRefGoogle Scholar
  17. Nishimura Y (2004) Rationale for chemoradiotherapy. Int J Clin Oncol 9:414–420PubMedCrossRefGoogle Scholar
  18. Noll S, Kralj M, Suman L, Stephan H, Piantanida I (2009) Synthesis of modified pyrimidine bases and positive impact of chemically reactive substituents on their in vitro antiproliferative activity. Eur J Med Chem 44:1172–1179PubMedCrossRefGoogle Scholar
  19. Said SA, Amr AE, Sabry NM, Abdalla MM (2009) Analgesic, anticonvulsant and anti-inflammatory activities of some synthesized benzodiazepine, triazolopyrimidine and bis-imide derivatives. Eur J Med Chem 44(12):4787–4792PubMedCrossRefGoogle Scholar
  20. Skehan P, Storeng R (1990) New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer Inst 82:1107–1112PubMedCrossRefGoogle Scholar
  21. Supuran CT, Scozzafava A (2007) Carbonic anhydrases as targets for medicinal chemistry. Bioorg Med Chem 15(13):4336–4350PubMedCrossRefGoogle Scholar
  22. Supuran CT, Innocenti A, Mastrolorenzo A, Scozzafava A (2004) Antiviral sulfonamide derivatives. Mini Rev Chem 4(2):189–200CrossRefGoogle Scholar
  23. Temperini C, Scozzafava A, Supuran CT (2010) Carbonic anhydrase inhibitors. X-ray crystal studies of the carbonic anhydrase II-trithiocarbonate adduct-An inhibitor mimicking the sulfonamide and urea binding to the enzyme. Bioorg Med Chem Lett 20(2):474–478PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Mostafa M. Ghorab
    • 1
  • Fatma A. Ragab
    • 2
  • Helmy I. Heiba
    • 3
  • Hanan A. Youssef
    • 2
  • Marwa G. El-Gazzar
    • 3
  1. 1.Medicinal, aromatic and poisonous plants research center (MAPPRC)College of pharmacy, King Saud UniversityRiyadhSaudi Arabia
  2. 2.Department of Pharmaceutical ChemistryFaculty of Pharmacy, Cairo UniversityCairoEgypt
  3. 3.Department of Drug Radiation ResearchNational Center for Radiation, Research and TechnologyNasr City, CairoEgypt

Personalised recommendations