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

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
• 2 Hawkins MA, Dawson LA. Radiation therapy for hepatocellular carcinoma from palliation to cure. Cancer 2006; 106: 1653-61
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 16 Drews J. Drug discovery: a historical perspective. Science. 2000; 287: 1960-4
• 17 Supuran CT, Scozzafava A. Carbonic anhydrase inhibitors. Curr Med Chem. 2001; 1: 61-97
• 18 Maren TH. Relatins between structure and biological activity of sulfonamides. Annu Rev Pharmacol Toxicol. 1976; 16: 309-27
• 19 Boyd AE. Sulfonylurea receptors, ion channels, and fruit flies. Diabetes. 1988; 37: 847-50
• 20 Thornber CW. Isosterism and molecular modification in drug design. Chem Soc Rev. 1979; 8: 563-80
• 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
• 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
• 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
• 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
• 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
• 26 Vokes EE, Weichselbaum RR. Concomitant chemoradiotherapy: rationale and clinical experience in patients with solid tumors. J Clin Oncol. 1990; 8: 911-34
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 34 Nishimura Y. Rational chemoradiotherapy. Int J Clin Oncol. 2004; 9: 414-20