Download PDF
Arzneimittelforschung 2011; 61(12): 719-726
DOI: 10.1055/s-0031-1300593
Antibiotics · Antimycotics · Antiparasitics · Antiviral Drugs · Chemotherapeutics · Cytostatics
Editio Cantor Verlag Aulendorf (Germany)

Utility of methyl 2-isothiocyanatobenzoate in the synthesis of some new quinazoline derivatives as potential anticancer and radiosensitizing agents

Mostafa M. Ghorab
1   Medicinal, Aromatic and Poisonous Plants Research Center, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
,
Fatma A. Ragab
2   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt
,
Helmi I. Heiba
3   Department of Drug Radiation Research, National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt
,
Ahmad A. Bayomi
3   Department of Drug Radiation Research, National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt
› Author Affiliations
Further Information

Publication History

Publication Date:
09 February 2012 (online)

    Permissions and Reprints

Abstract

Novel quinazolines 4–11, 15 and triazoloquinazolines 12–14 bearing biologically active sulfonamide moieties were synthesized. All the newly synthesized compounds were evaluated for their in vitro anticancer activity against liver cancer cell line (HEPG2). Some of the screened compounds exhibited interesting cytotoxic activity compared to doxorubicin as a reference drug. The most active compounds 13 and 15 were selected and evaluated for their ability to enhance the cell killing effect of γ-radiation, compound 15 was superior to doxorubicin in radiation combination therapy.

Key words

Anticancer drugs - Quinazolines - Radiosensitizers - Sulfonamides
 

  • References

  • 1 Lau WY, Lai ECH. Hepatocellular carcinoma: current management and recent advances. Hepatobiliary Pancreat Dis Int. 2008; 7: 237-57
    PubMedGoogle Scholar
  • 2 Hawkins MA, Dawson LA. Radiation therapy for hepatocellular carcinoma from palliation to cure. Cancer 2006; 106: 1653-61
    CrossrefPubMedGoogle Scholar
  • 3 Höpfner M, Sutter Ap, Huether A, Schuppan D, Zeitz M, Scherübl H. Targeting the epidermal growth factor receptor by gefitinib for treatment of hepatocellular carcinoma. J Hepatol. 2004; 41: 1008-16
    CrossrefPubMedGoogle Scholar
  • 4 Liu Y, Poon RTP, Shao W, Sun X, Chen H, Kok TW et al. Blockage of epidermal growth factor receptor by quinazoline tyrosine kinase inhibitors suppresses growth of human hepatocellular carcinoma. Cancer Lett. 2007; 248: 32-40
    CrossrefPubMedGoogle Scholar
  • 5 Schiffer E, Housset C, Cacheux W, Wendum D, Desbois-Mouthon C, Rey C. Gefitinib, an EGFR inhibitor, prevents hepatocellular carcinoma development in the rat liver with cirrhosis. Hepatology. 2005; 41: 307-14
    CrossrefPubMedGoogle Scholar
  • 6 Ramadori G, Fuzesi L, Grabbe E, Pieler T, Armbrust T. Successful treatment of hepatocellular carcinoma with the tyrosine kinase inhibitor imatinib in a patient with liver cirrhosis. Anticancer Drugs. 2004; 15: 405-9
    CrossrefPubMedGoogle Scholar
  • 7 Matsuo J, Sakurai H, Saiki I. ZD1839, a selective epidermal growth factor receptor tyrosine kinase inhibitor, shows antimetastatic activity using a hepatocellular carcinoma model. Mol Cancer Ther. 2003; 2: 557-61
    PubMedGoogle Scholar
  • 8 Al-Rashood ST, Aboldahab IA, Nagi MN, Abouzeid LA, Abdel-Aziz AAM, Abdel-hamide SG et al. Synthesis, dihydro-folate reductase inhibition, antitumor testing, and molecular modeling study of some new 4(3H)-quinazolinone analogs. Bioorg Med Chem. 2006; 14: 8608-21
    CrossrefPubMedGoogle Scholar
  • 9 Jin Y, Zhou ZY, Tian W, Yu Q, Long YQ. 4’-Alkoxy substitution enhancing the anti-mitotic effect of 5-(3’,4’,5’-substituted)aniline-4-hydroxy-8-nitroquinazolines as a novel class of anti-microtubule agents. Bioorg Med Chem Lett. 2006; 16: 5864-9
    CrossrefPubMedGoogle Scholar
  • 10 Ballard P, Bradbury RH, Harris CS, Hennequin LFA, Hickinson M, Johnson PD et al. Inhibitors of epidermal growth factor receptor tyrosine kinase: novel C-5 substituted anili-noquinazolines designed to target the ribose pocket. Bioorg Med Chem Lett. 2006; 16: 1633-7
    CrossrefPubMedGoogle Scholar
  • 11 Bathini Y, Singh I, Harvey PJ, Keller PR, Singh R, Micetich RG et al. 2-Aminoquinazoline inhibitors of cyclin-dependent kinases. Bioorg Med Chem Lett. 2005; 15: 3881-5
    CrossrefPubMedGoogle Scholar
  • 12 Baversias V, Bisset GMF, Kimbell R, Boyle FT, Jackman AL. Synthesis of novel quinazoline-based antifolates with modified glutamate side chains as potential inhibitors of thymidylate synthase and antitumor agents. Tetrahedron. 1997; 53: 13383-96
    CrossrefPubMedGoogle Scholar
  • 13 Ballard P, Bradbury RH, Hennequin LFA, Hickinson DM, Johnson PD, Kettle JG et al. 5-Substituted 4-anilinoquinazolines as potent, selective and orally active inhibitors of erbB2 receptor tyrosine kinase. Bioorg Med Chem Lett. 2005; 15: 4226-9
    CrossrefPubMedGoogle Scholar
  • 14 Barlaam B, Fennell M, Germain H, Green T, Hennequin L, Morgentin R et al. New heterocyclic analogues of 4-(2-chloro-5-methoxyanilino)quinazolines as potent and selective c-Src kinase inhibitors. Bioorg Med Chem Lett. 2005; 15: 5446-9
    CrossrefPubMedGoogle Scholar
  • 15 Zache N, Lambert JMR, Rökaeus N, Shen J, Hainaut P, Bergman J et al. Mutant p53 targeting by the low molecular weight compound STIMA-1. Molec Oncol. 2008; 2: 70-80
    PubMedGoogle Scholar
  • 16 Drews J. Drug discovery: a historical perspective. Science. 2000; 287: 1960-4
    CrossrefPubMedGoogle Scholar
  • 17 Supuran CT, Scozzafava A. Carbonic anhydrase inhibitors. Curr Med Chem. 2001; 1: 61-97
    PubMedGoogle Scholar
  • 18 Maren TH. Relatins between structure and biological activity of sulfonamides. Annu Rev Pharmacol Toxicol. 1976; 16: 309-27
    CrossrefPubMedGoogle Scholar
  • 19 Boyd AE. Sulfonylurea receptors, ion channels, and fruit flies. Diabetes. 1988; 37: 847-50
    CrossrefPubMedGoogle Scholar
  • 20 Thornber CW. Isosterism and molecular modification in drug design. Chem Soc Rev. 1979; 8: 563-80
    CrossrefPubMedGoogle Scholar
  • 21 Alqasoumi SI, Al-Taweel AM, Alafeefy AM, Noaman E, Ghorab MM. Novel quinolines and pyrimido[4,5-b]quinolines bearing biologically active sulfonamide moiety as a new class of antitumor agents. Eur J Med Chem. 2010; 45: 738-44
    CrossrefPubMedGoogle Scholar
  • 22 Al-Said MS, Ghorab MM, Alqasoumi SI, El-Hossary EM, Noaman E. Synthesis and in vitro anticancer screening of some novel 4-[2-amino-3-cyano-4-substituted-5,6,7,8-tet-rahydroquinolin-l-(4H)-yl]benzenesulfonamides. Eur J Med Chem. 2010; 45: 3011-8
    CrossrefPubMedGoogle Scholar
  • 23 Ghorab MM, Ragab FA, Hamed MM. Design, synthesis and anticancer evaluation of novel tetrahydroquinoline derivatives containing sulfonamide moiety. Eur J Med Chem. 2009; 44: 4211-7
    CrossrefPubMedGoogle Scholar
  • 24 Alqasoumi SI, Al-Taweel AM, Alafeefy AM, Ghorab MM, Noaman E. Discovering some novel tetrahydroquinoline derivatives bearing the biologically active sulfonamide moiety as a new class of antitumor agents. Eur J Med Chem. 2010; 45: 1849-53
    CrossrefPubMedGoogle Scholar
  • 25 Magné N, Chargari C, Soria JC, Deutsch E. Concomitant chemoradiotherapy in clinical trials: To promote step by step rational development. Crit Rev Oncol Hematol. 2009; 70: 206-15
    CrossrefPubMedGoogle Scholar
  • 26 Vokes EE, Weichselbaum RR. Concomitant chemoradiotherapy: rationale and clinical experience in patients with solid tumors. J Clin Oncol. 1990; 8: 911-34
    PubMedGoogle Scholar
  • 27 Yang LX, Douple EB, O’Hara JA, Wang HJ. Production of DNA double-strand breaks by interactions between carboplatin and radiation: a potential mechanism for radiopo-tentiation. Radiat Res. 1995; 143: 309-15
    CrossrefPubMedGoogle Scholar
  • 28 Hennequin C, Giocanti N, Balosso J, Favaudon V. Interaction of ionizing radiation with the topoisomerase I poison camptothecin in growing V-79 and Hela cells. Cancer Res. 1994; 54: 1720-8
    PubMedGoogle Scholar
  • 29 Liu F, Wang JJ, You ZY, Zhang YD, Zhao Y. Radiosensitivity of prostate cancer cells is enhanced by EGFR inhibitor C225. Urol Oncol. 2010; 28: 59-66
    CrossrefPubMedGoogle Scholar
  • 30 Krause M, Ostermann G, Petersen C. Decreased repopulation as well as increased reoxygenation contribute to the improvement in local control after targeting of the EGFR by C225 during fractionated irradiation. Radiother Oncol. 2005; 76: 162-7
    CrossrefPubMedGoogle Scholar
  • 31 Williams KJ, Telfer BA, Shannon AM, Babur M, Stratford IJ, Wedge SR. Combining radiotherapy with AZD2171, a potent inhibitor of vascular endothelial growth factor signaling: pathophysiologic effects and therapeutic benefit. Mol Cancer Ther. 2007; 6: 599-606
    CrossrefPubMedGoogle Scholar
  • 32 Santagati A, Modica M, Santagati M, Cutuli VMC, Mangano NG, Caruso A. Synthesis and pharmacological screening of l,3,4-thiadiazino[2,3-b]quinazoline derivatives. Pharmazie. 2000; 55: 500-2
    PubMedGoogle Scholar
  • 33 Skehan P, Storeng R, Scudiero D, Monks A, McMahon J, Vistica D et al. New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer Inst. 1990; 82: 1107-12
    CrossrefPubMedGoogle Scholar
  • 34 Nishimura Y. Rational chemoradiotherapy. Int J Clin Oncol. 2004; 9: 414-20
    CrossrefPubMedGoogle Scholar