Antitumor activity of 6-substituted derivatives of 4-alkylaminoquinazolines

Authors

  • V. M. Sapelkin Institute of Molecular Biology and Genetics, NAS of Ukraine 150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680 Author
  • I. E. Makovenko Institute of Molecular Biology and Genetics, NAS of Ukraine 150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680 Author
  • S. S. Lukashov Institute of Molecular Biology and Genetics, NAS of Ukraine 150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680 Author
  • G. G. Dubinina Institute of Molecular Biology and Genetics, NAS of Ukraine 150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680 Author
  • S. M. Yarmoluk Institute of Molecular Biology and Genetics, NAS of Ukraine 150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680 Author

DOI:

https://doi.org/10.7124/bc.000677

Abstract

13 derivatives of 6-R-4-alkylaminoauinazoline were synthesized and tested for antitumor activity (in vitro). According to the resultes of testing with 56 human tumor cell lines four compounds 4.1, 4.9–4.11 were shown to inhibit the proliferation of cancer cells at low micromotor concentrations, 1-phenylethylf 4 quinuzolinylfamine (4.1) exhibits antitumor activity: GI50– 2.29 μ; LC50 –46.7mkM (cell line SK-MFL-5 (Melanoma)); the 6-bromo4 auinazolinyKtert-butyDamine (4. to): GI50 3 82 μM; LC50 –43.7 μM (cell line SK-MEl.-S (Melanoma)) and GI50 –2.64 μM, LC50– 44.2 μM (cell line CAKI-l (Renal Cancer)).

References

Sielecki TM, Boylan JF, Benfield PA, Trainor GL. Cyclin-dependent kinase inhibitors: useful targets in cell cycle regulation. J Med Chem. 2000;43(1):1-18.

Smaill JB, Palmer BD, Rewcastle GW, Denny WA, McNamara DJ, Dobrusin EM, Bridges AJ, Zhou H, Showalter HD, Winters RT, Leopold WR, Fry DW, Nelson JM, Slintak V, Elliot WL, Roberts BJ, Vincent PW, Patmore SJ. Tyrosine kinase inhibitors. 15. 4-(Phenylamino)quinazoline and 4-(phenylamino)pyrido[d]pyrimidine acrylamides as irreversible inhibitors of the ATP binding site of the epidermal growth factor receptor. J Med Chem. 1999;42(10):1803-15.

Wakeling AE, Barker AJ, Davies DH, Brown DS, Green LR, Cartlidge SA, Woodburn JR. Specific inhibition of epidermal growth factor receptor tyrosine kinase by 4-anilinoquinazolines. Breast Cancer Res Treat. 1996;38(1):67-73.

Liu XG, Liang NC. Inhibitory effect and its kinetic analysis of tyrphostin AG1478 on recombinant human protein kinase CK2 holoenzyme. Acta Pharmacol Sin. 2002;23(6):556-61.

Tamura T. [Molecular target-based cancer therapy: epidermal growth factor receptor inhibitors]. Nihon Geka Gakkai Zasshi. 2002;103(2):233-6.

Ciardiello F, Caputo R, Bianco R, Damiano V, Pomatico G, De Placido S, Bianco AR, Tortora G. Antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by ZD-1839 (Iressa), an epidermal growth factor receptor-selective tyrosine kinase inhibitor. Clin Cancer Res. 2000;6(5):2053-63.

Wissner A, Brawner Floyd MB, Rabindran SK, Nilakantan R, Greenberger LM, Shen R, Wang YF, Tsou HR. Syntheses and EGFR and HER-2 kinase inhibitory activities of 4-anilinoquinoline-3-carbonitriles: analogues of three important 4-anilinoquinazolines currently undergoing clinical evaluation as therapeutic antitumor agents. Bioorg Med Chem Lett. 2002;12(20):2893-7.

Slichenmyer WJ, Fry DW. Anticancer therapy targeting the erbB family of receptor tyrosine kinases. Semin Oncol. 2001;28(5 Suppl 16):67-79.

Teitze LF, Eicher T. Reaktionen und Synthesen im organisch-chemischen Praktikum und Forschungslaboratorium . Georg Thieme Verlag Stuttgart New York 1991

Zhungietu EI, Rekhter MA. Isatin and its derivatives. Kishinev: Shtiintsa, 1977. 229 p.

Amarego WLF. Preparation of phthalazine and quinazoline. J Appl Chem. 1961; (11):70-2.

Published

2003-09-20

Issue

Section

Bioorganic Chemistry