Skip to main content
SpringerLink
Log in

Novel 4-(4-substituted-thiazol-2-ylamino)-N-(pyridin-2-yl)-benzenesulfonamides as cytotoxic and radiosensitizing agents

  • Research Article
  • Drug Design and Discovery
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

A series of novel 4-(4-substituted-thiazol-2-ylamino)-N-(pyridin-2-yl) benzene-sulfonamides were synthesized and screened for their cytotoxic activity against human breast cancer cell line (MCF-7). Compounds 6, 7, 9, 10, 11, and 14 displayed significant activity against MCF-7 when compared to doxorubicin, which was used as a reference drug. The synergistic effect of Gamma radiation for the most active derivatives 7, 9, and 11 was also studied and their IC50 values markedly decreased to 11.9 μM, 11.7 μM, and 11.6 μM, respectively.

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

  • Abbate, F., Casini, A., Owa, T., Scozzafava, A., and Supuran, C. T., Carbonic anhydrase inhibitors: E7070, a sulfonamide anticancer agent, potently inhibits cytosolic isozymes I and II, and transmembrane, tumor-associated isozyme IX. Bioorg. Med. Chem. Lett., 14, 217–223 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Al-Said, M. S., Ghorab, M. M., Al-qasoumi, S. I., El-Hossary, E. M., and Noaman, E., Synthesis and in vitro anticancer screening of some novel 4-[2-amino-3-cyano-4-substituted-5,6,7,8-tetrahydroquinolin-1-(4H)-yl] Benzenesulfonamides. Eur. J. Med. Chem., 45, 3011–3018 (2010).

    Article  PubMed  CAS  Google Scholar 

  • Casini, A., Scozzafava, A., Mastrolorenzo, A., and Supuran, C. T., Sulfonamides and sulfonylated derivatives as anticancer agents. Curr. Cancer Drug Tar., 2, 55–75 (2002a).

    Article  CAS  Google Scholar 

  • Casini, A., Scozzafava, A., and Supuran, C. T., Sulfonamide derivatives with protease inhibitory action as anticancer, anti-inflammatory and antiviral agents. Expert Opin. Ther. Pat., 12, 1307–1327 (2002b).

    Article  CAS  Google Scholar 

  • Davis, S. T., Benson, B. G., Bramson, H. N., Chapman, D. E, Dickerson, S. H., Dold, K. M., Eberwein, D. J., Edelstein, M., Frye, S. V., Gampe, R. T., Jr., Griffin, R.J., Harris, P. A., Hassell, A. M., Holmes, W. D., Hunter, R. N., Knick, V. B., Lackey, K., Lovejoy, B., Luzzio, M. J., Murray, D., Parker, P., Rocque, W. J., Shewchuk, L., Veal, J. M., Walker, D. H., and Kuyper, L. F., Prevention of chemotherapy-induced alopecia in rats by CDK inhibitors. Science, 291, 134–137 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Finkelstein, J., N4-Substituted Sulfonamides. J. Am. Chem. Soc., 66, 407–408 (1944).

    Article  CAS  Google Scholar 

  • Fischer, P. M. and Lane, D. P., Inhibitors of cyclin-dependent kinases as anti-cancer therapeutics. Curr. Med. Chem., 7, 1213–1245 (2000).

    PubMed  CAS  Google Scholar 

  • Fukuoka, K., Usuda, J., Iwamoto, Y., Fukumoto, H., Nakamura, T., Yoneda, T., Narita, N., Saijo, N., and Nishio, K., Mechanisms of action of the novel sulfonamide anticancer agent E7070 on cell cycle progression in human non-small cell lung cancer cells. Invest. New Drugs 19, 219–227 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Ghorab, M. M., Ragab, F. A., and Hamed, M. M., Synthesis of novel pyrrole and pyrrolo[2,3-d]pyrimidine derivatives bearing sulfonamide moiety for evaluation as anticancer and radiosensitizing agents. Arzneim. Forsch., 60, 141–148 (2010a).

    CAS  Google Scholar 

  • Ghorab, M. M., Ragab, F. A., Heiba, H. I., Arafa, R. K., and El-Hossary, E. M., Docking study, in vitro anticancer screening and radiosensitizing evaluation of some new fluorine-containing quinoline and pyrimidoquinoline derivatives bearing a sulfonamide moiety. Med. Chem. Res., 20, 388–400 (2011).

    Article  CAS  Google Scholar 

  • Ghorab, M. M., Ragab, F. A., Heiba, H. I., Youssef, H. A., and El-Gazzar, M. G., Synthesis of novel pyrrole and pyrrolo[2,3-d]pyrimidine derivatives bearing sulfonamide moiety for evaluation as anticancer and radiosensitizing agents. Bioorg. Med. Chem. Lett., 20, 6316–6320 (2010b).

    Article  PubMed  CAS  Google Scholar 

  • Ghorab, M. M., Ragab, F. A., Heiba, H. I., Youssef, H. A., and El-Gazzar, M. G., Synthesis of some new pyrazole and pyrimidine derivatives carrying a sulfonamide moiety of expected antitumor activity and study of the synergistic effect of gamma-irradiation. Arzneim. Forsch., 60, 48–55 (2010c).

    CAS  Google Scholar 

  • Ghorab, M. M., Noaman, E., Ismail, M. M., Heiba, H. I., Ammar, Y. A., and Sayed, M. Y., Novel antitumor and radioprotective sulfonamides containing pyrrolo[2,3-d]pyrimidines. Arzneim. Forsch., 56, 405–413 (2006).

    CAS  Google Scholar 

  • Ghorab, M. M., Ragab, F. A., and Hamed, M. M., Design, synthesis and anticancer evaluation of novel tetrahydroquinoline derivatives containing sulfonamide moiety. Eur. J. Med. Chem., 44, 4211–4217 (2009).

    Article  PubMed  CAS  Google Scholar 

  • Honda, R., Lowe, E. D., Dubinina, E., Skamnaki, V., Cook, A., Brown, N. R., and Johnson, L. N., The structure of cyclin E1/CDK2: implications for CDK2 activation and CDK2-independent roles. EMBO J., 24, 452–263 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Huang, S., Connolly, P. J., Lin, R., Emanuel, S., and Middleton, S. A., Synthesis and evaluation of N-acyl sulfonamides as potential prodrugs of cyclin-dependent kinase inhibitor JNJ-7706621. Bioorg. Med. Chem. Lett., 16, 3639–3641 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Ismail, M. M., Ghorab, M. M., Noaman, E., Ammar, Y. A., Heiba, H. I., and Sayed, M. Y., Novel synthesis of pyrrolo [2,3-d]pyrimidines bearing sulfonamide moieties as potential antitumor and radioprotective agents. Arzneim. Forsch., 56, 301–308 (2006).

    CAS  Google Scholar 

  • Jeffrey, P. D., Russo, A. A., Polyak, K., Gibbs, E., Hurwitz, J., Massague, J., and Pavletich, N. P., Mechanism of CDK activation revealed by the structure of a cyclin A-CDK2 complex. Nature, 376, 313–320 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Kamel, M. M., Ali, H. I., Anwar, M. M., Mohameda, N. A., and Soliman, M. A., Synthesis, antitumor activity and molecular docking study of novel Sulfonamide-Schiff’s bases, thiazolidinones, benzothiazinones and their C-nucleoside derivatives. Eur. J. Med. Chem., 45, 572–580 (2010).

    Article  PubMed  CAS  Google Scholar 

  • Kawai, M., BaMaung, N. Y., Fidanze, S. D., Erickson, S. A., Tedrow, J. S., Sanders, W. J., Vasudevan, A., Park, C., Hutchins, C., Comess, K. M., Kalvin, D., Wang, J., Zhang, Q., Lou, P., Tucker-Garcia, L., Bouska, J., Bell, R. L., Lesniewski, R., Henkin, J., and Sheppard, G. S., Development of sulfonamide compounds as potent methionine aminopeptidase type II inhibitors with antiproliferative properties. Bioorg. Med. Chem. Lett., 16, 3574–3577 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Kenneth, R., Hande, K. R., Hagey, A., Berlin, J., Cai, Y., Meek, K., Kobayashi, H., Lockhart, A. C., Medina, D., Sosman, J., Gordon, G. B., and Rothenberg, M. L., The Pharmacokinetics and Safety of ABT-751, a Novel, Orally Bioavailable Sulfonamide Antimitotic Agent: Results of a Phase 1 Study. Clin. Cancer Res., 12, 2834 (2006).

    Article  Google Scholar 

  • Kesteren, C. V., Mathôt, R. A. A., Raymond, E., Armand, J. P., Dittrich, C., Dumez, H., Roché, H., Droz, J. P., Punt, C., Ravic, M., Wanders, J., Beijnen, J. H., and Fumoleau, P., Schellens for the Early Clinical Studies Group of the European Organization for Research and Treatment of Cancer. J. Clin. Oncol., 20, 4065–4073 (2002).

    Article  PubMed  Google Scholar 

  • Lucking, U., Siemeister, G., Schafer, M., Briem, H., Kruger, M., Lienau, P., and Jautelat, R., Macrocyclic aminopyrimidines as multitarget CDK and VEGF-R inhibitors with potent antiproliferative activities. Chem. Med. Chem., 2, 63–77 (2007).

    PubMed  Google Scholar 

  • Morgan, D. O., Cyclin-Dependent Kinases. The Cell Cycle: Principles of Control. Online: New Science Press Ltd. http://www.new-science-press.com/content/pdf/nsp-cellcycle-3-1.

  • Nishimura, Y., Rational of chemotherapy. Int. J. Clin. Oncol., 9, 414–420 (2004).

    Article  PubMed  Google Scholar 

  • Payne, J. E., Bonnefous, C., Hassig, C. A., Symons, K. T., Guo, X., Nguyen, P. M., Annable, T., Wash, P. L., Hoffman, T. Z., Rao, T. S., Shiau, A. K., Malecha, J. W., Noble, S. A., Hager, J. H., and Smith, N. D., Identification of KD5170: A novel mercaptoketone-based histone deacetylase inhibitor. Bioorg. Med. Chem. Lett., 18, 6093–6096 (2008).

    Article  PubMed  CAS  Google Scholar 

  • Richardson, C. M., Nunns, C. L., Williamson, D. S., Parratt, M. J., Dokurno, P., Howes, R., Borgognoni, J., Drysdale, M. J., Finch, H., Hubbard, R. E., Jackson, P. S., Kierstan, P., Lentzen, G., Moore, J. D., Murray, J. B., Simmonite, H., Surgenor, A. E., and Torrance, C. J., Discovery of a potent CDK2 inhibitor with a novel binding mode, using virtual screening and initial, structure-guided lead scoping. Bioorg. Med. Chem. Lett., 17, 3880–3885 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Skehan, P., Storeng, R., Scudiero, D., Monks, A., McMahon, J., Vistica, D., Warren, J. T., Bokesch, H., Kenney, S., and Boyd, M. R., New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer Inst., 82, 1107–1112 (1990).

    Article  PubMed  CAS  Google Scholar 

  • Supuran, C. T. and Scozzafava, A., Carbonic anhydrase inhibitors and their therapeutic potential. Expert Opin. Ther. Pat., 10, 575–600 (2000).

    Article  CAS  Google Scholar 

  • Supuran, C. T., Briganti, F., Tilli, S., Chegwidden, W. R., and Scozzafava, A., Carbonic anhydrase inhibitors: Sulfonamides as antitumoragents. Bioorgan. Med. Chem., 9, 703–714 (2001).

    Article  CAS  Google Scholar 

  • Villar, R., Encio, I., Migliaccio, M., Gil, M. J., and Martinez-Merino, V., Synthesis and cytotoxic activity of lipophilic sulphonamide derivatives of the benzo[b]thiophene 1,1-dioxide. Bioorg. Med. Chem., 12, 963–968 (2004).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medicinal, Aromatic and Poisonous Plants Research Center (MAPPRC), College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia

    Mostafa M. Ghorab

  2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt

    Fatma A. Ragab & Yassin M. Nissan

  3. Department of Drug Radiation Research, National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt

    Helmy I. Heiba & Hebaallah M. Agha

Authors
  1. Mostafa M. Ghorab
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fatma A. Ragab
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Helmy I. Heiba
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hebaallah M. Agha
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yassin M. Nissan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mostafa M. Ghorab.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ghorab, M.M., Ragab, F.A., Heiba, H.I. et al. Novel 4-(4-substituted-thiazol-2-ylamino)-N-(pyridin-2-yl)-benzenesulfonamides as cytotoxic and radiosensitizing agents. Arch. Pharm. Res. 35, 59–68 (2012). https://doi.org/10.1007/s12272-012-0106-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12272-012-0106-y

Key words

Search

Navigation