Biopolym. Cell. 2003; 19(2):196-201.
http://dx.doi.org/10.7124/bc.00064E
Bioorganic Chemistry
Inhibitors of cyclin-dependent kinases. Synthesis of combinatorial libraries of 3-phenoxy-7-hydroxy-8-alkylaminomethylchromone derivatives and study on their anticancer activity
1Arkhipov V. V., 1Prikhod'ko A. O., 1Golub A. G., 2Khilya V. P., 1Yarmoluk S. M.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. Taras Shevchenko National University of Kyiv
    64, Volodymyrska Str., Kyiv, Ukraine, 01033

Abstract

Cyclin-dependent kinases (CDK) play an important role in the cell cycle regulation. CDK are used as targets in a search for anticancer drugs. This study was aimed at the synthesis of 3-aryloxy-7-hydroxy-8-alkylaminomethylchromone derivatives, potential inhibitors of CDK. The antitumor activity of the compounds synthesyzed has been tested using 60 human tumor cell lines. 4 of the compounds tested have been revealed to inhibit the tumor cells proliferation.
Full text: (PDF, in Ukrainian)

References

[1] Sielecki TM, Boylan JF, Benfield PA, Trainor GL. Cyclin-dependent kinase inhibitors: useful targets in cell cycle regulation. (2000) J Med Chem. 2000;43(1):1-18.
[2] Vasil'ev S.A., Luk'yanchikov M.S., Molchanov G.I., Turubarov V.D., Khilya V.P. Synthesis and biological properties of 3-phenoxchromones and 3-phenoxy-4-hydroxy-7-methoxycoumarin Pharmaceutical Chemistry Journal 1991; 25 (7) , pp. 470-475
[3] Ogorodnychuk A. S., Vassilyev S. A., Lekhan I. N., Khilya V. P., Shilyn V. V. Synthesis and properties of 3-fluorophenoxy-7-O-aminoacylchromones Russian Journal of Bioorganic Chemistry 1991; 17 (7):1005-1007
[4] Gorbulenko NV, Gaiduk OV, Ogorodnychuk AS, Khilya VP, Shilin VV. Amino-Acid derivatives of benzimidazole analogues of isoflavones. Doklady Akad Nauk Ukr SSR. 1991;(9):144-8
[5] Graziani Y, Erikson E, Erikson RL. The effect of quercetin on the phosphorylation activity of the Rous sarcoma virus transforming gene product in vitro and in vivo (1983) Eur J Biochem. 1983;135(3):583-9.
[6] Fischer PM, Lane DP. Inhibitors of cyclin-dependent kinases as anti-cancer therapeutics. Curr Med Chem. 2000;7(12):1213-45.
[7] Gray NS, Wodicka L, Thunnissen AM, Norman TC, Kwon S, Espinoza FH, Morgan DO, Barnes G, LeClerc S, Meijer L, Kim SH, Lockhart DJ, Schultz PG. Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors. Science. 1998;281(5376):533-8.
[8] Zaharevitz DW, Gussio R, Leost M, Senderowicz AM, Lahusen T, Kunick C, Meijer L, Sausville EA. Discovery and initial characterization of the paullones, a novel class of small-molecule inhibitors of cyclin-dependent kinases. Cancer Res. 1999;59(11):2566-9.
[9] Lawrie AM, Noble ME, Tunnah P, Brown NR, Johnson LN, Endicott JA. Protein kinase inhibition by staurosporine revealed in details of the molecular interaction with CDK2. Nat Struct Biol. 1997;4(10):796-801.
[10] Hoessel R, Leclerc S, Endicott JA, Nobel ME, Lawrie A, Tunnah P, Leost M, Damiens E, Marie D, Marko D, Niederberger E, Tang W, Eisenbrand G, Meijer L. Indirubin, the active constituent of a Chinese antileukaemia medicine, inhibits cyclin-dependent kinases. Nat Cell Biol. 1999;1(1):60-7
[11] Nugiel DA, Etzkorn AM, Vidwans A, Benfield PA, Boisclair M, Burton CR, Cox S, Czerniak PM, Doleniak D, Seitz SP. Indenopyrazoles as novel cyclin dependent kinase (CDK) inhibitors. J Med Chem. 2001;44(9):1334-6.
[12] Walker DH. Small-molecule inhibitors of cyclin-dependent kinases: molecular tools and potential therapeutics. Curr Top Microbiol Immunol. 1998;227:149-65.
[13] Senderowicz AM, Headlee D, Stinson SF, Lush RM, Kalil N, Villalba L, Hill K, Steinberg SM, Figg WD, Tompkins A, Arbuck SG, Sausville EA. Phase I trial of continuous infusion flavopiridol, a novel cyclin-dependent kinase inhibitor, in patients with refractory neoplasms. J Clin Oncol. 1998;16(9):2986-99.
[14] Arkhipov V. V., Smirnov M. N., Khilya V. P. Chemistry of modified flavonoids Chemistry of Heterocyclic Compounds 1997, 33(5) pp 515-519
[15] Garazd M. M. , Arkhipov V. V., Proskurka N. K., Khilya V. P. Chemistry of heteroanalogs of isoflavones. 23. Synthesis of aminoacyl derivatives of 3-phenoxychromone Chemistry of Heterocyclic Compounds Jue 1999, 35(6), pp 658-662