Abstract
In an effort to detect potential inhibitors of cdc25 phosphatase, nineteen flavonoids
belonging to the quercetin and kaempferol series have been evaluated, using a colorimetric
assay of recombinant human cdc25A tyrosine phosphatase as a cell cycle-specific target.
Compounds bearing two benzyl or methyl groups in positions 7 and 4′ and acetyl on
the hydroxy groups of the sugar moiety showed the maximal activity.
References
1
Hengst L, Dulic V, Slingerland J M, Lees E, Reed S T.
A cell cycle-regulated inhibitor of cyclin-dependent kinanes.
Proceedings of the National Academy of Sciences of the United States of America.
1994;
91
5291-5
2
Murray A W, Kirschner M W.
Dominoes and clocks: the union of two views of the cell cycle.
Science.
1989;
246
614-21
3
Nurse P.
Universal control mechanism regulating onset of M-phase.
Nature.
1990;
344
503-8
4
Baratte B, Meijer L, Galactionov K, Beach D.
Screening for antimitotic compounds using the cdc25 tyrosine phosphatase, an activator
of the mitosis-inducing p34cdc2 /cyclin Bcdc13 protein kinase.
Anticancer Research.
1992;
12
873-80
5
Rosenblatt J, De Bondt H, Jancarik J, Morgan D O, Kim S-H.
Purification and crystallization of human cyclin-dependent kinase 2.
The Journal of Molecular Biology.
1993;
230
1317-9
6
Forsburg S L, Nurse P.
Cell cycle regulation in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe
.
Annual Reviews of Cell Biology.
1991;
7
227-56
7
Lee M G, Nurse P.
Complementation used to clone a human homologue of the fission yeast cell cycle control
gene cdc2.
Nature.
1987;
327
31-5
8
Pines J, Hunter T.
Isolation of a human cyclin cDNA: evidence for cyclin mRNA and protein regulation
in the cell cycle and for interaction with p34cdc2.
Cell.
1989;
58
833-46
9
Rialet V, Meijer L.
A new screening test for antimitotic compounds using the universal M phase-specific
protein kinase, p34cdc2 /cyclin Bcdc13 , affinity-immobilized on p13suc1 -coated microtitration plates.
Anticancer Research.
1990;
11
1581-90
10
Vesely J, Havlicek L, Strnad M, Blow J J, Donella-Deana A, Pinna L, Letham D S, Kato J,
Detivaud L, Leclerc S, Meijer L.
Inhibition of cyclin-dependent kinases by purine analogues.
European. Journal of the Biochemistry.
1994;
224
771-86
11
Sherr C J.
Mammalian G1 cyclins.
Cell.
1993;
73
1059-65
12
Traganos F, Ardelt B, Halko N, Bruno S, Darzynkiewicz Z.
Effects of genistein on the growth and cell cycle progression of normal human lymphocytes
and human leukmic MOLT-4 and HL-60 cells.
Cancer Research.
1992;
52
6200-8
13
Akiyama T, Ishida J, Nakagawa S, Ogawara H, Watanabe S, Itoh N, Shibuya M, Fuami Y.
Genistein, a specific inhibitor of tyrosine-specific protein kinases.
The Journal of Biological Chemistry.
1987;
262
5592-5
14
Yoshida M, Yamamoto M, Nikaido T.
Quercetin arrests human leukemic T-cells in late G1 phase of the cell cycle.
Cancer Research.
1992;
52
6676-81
15
Matsukawa Y, Marui N, Sakai T, Satomi Y, Yoshida M, Matsumoto K, Nishino H, Aoike A.
Genistein arrests cell cycle progression at G2-M.
Cancer Research.
1993;
53
1328-31
16
De Azevedo W F, Mueller-Dieckmann H-J, Schulze-Gahmen U, Worland P J, Sausville E,
Kim S-H.
Structural basis for specifity and potency of a flavonoid inhibitor of human CDK2,
a cell cycle Kinase.
Proceedings of the National Academy of Sciences of the United States of America.
1996;
93
2735-40
17
Losiewicz M D, Carlson B A, Kaur G, Sausville E A, Worland P J.
Potent inhibition of cdc2 kinase activity by the flavonoid L86-8275.
Biochemical and Biophysical Research Communications.
1994;
201
589-95
18
Mitrocotsa D, Mitaku S, Demetzos C, Harvala C, Mentis A, Perez S, Kokkinopoulos D.
Bioactive compounds from the buds of Platanus orientalis and isolation of a new kaempferol glycoside.
Planta Medica.
1993;
59
517-20
19
Jurd L, The selective alkylation of polyphenols. Methylation of 7-, 4′-, and 3′-hydroxy
groups in flavonols.
The Journal of Organic Chemistry.
1962;
27
1294-7
20
Demetzos C, Skaltsounis A L, Tillequin F, Koch M.
Phase-transfer-catalyzed synthesis of flavonoid glycosides.
Carbohydrate Research.
1990;
207
131-7
21
Gray N, Detivaud L, Doerig C, Meijer L.
ATP-site directed inhibitors of cyclin-dependent kinases.
Current Medicinal Chemistry.
1999;
6
1-17
Prof. S. Mitaku
Division of Pharmacognosy
School of Pharmacy
University of Athens
Panepistimiopolis Zografou
Athens 15771
Greece
eMail: mitakou@pharm.uoa.gr
Fax: 017274594