Zebularine: A unique molecule for an epigenetically based strategy in cancer chemotherapy

被引：67

作者：

Marquez, VE ^{[1
]}

Kelley, JA

Agbaria, R

Ben-Kasus, T

Cheng, JC

Yoo, CB

Jones, PA

机构：

[1] NCI, Canc Res Ctr, Med Chem Lab, NIH, Frederick, MD 21702 USA

[2] Ben Gurion Univ Negev, Fac Hlth Sci, Dept Clin Pharmacol, IL-84105 Beer Sheva, Israel

[3] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Urol, Los Angeles, CA 90089 USA

[4] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Biochem, Los Angeles, CA 90089 USA

[5] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Biol Mol, Los Angeles, CA 90089 USA

来源：

THERAPEUTIC OLIGONUCLEOTIDES: TRANSCRIPTIONAL AND TRANSLATIONAL STRATEGIES FOR SILENCING GENE EXPRESSION | 2005年 / 1058卷

关键词：

zebularine; cytidine deaminase inhibition; DNA methyltrasferase inhibition; antitumor activity; gene reactivation;

D O I：

10.1196/annals.1359.037

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

1-(beta-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one (zebularine) corresponds structurally to cytidine minus the exocyclic 4-amino group. The increased electrophilic character of its simple aglycon endows the molecule with unique biologic properties as a potent inhibitor of both cytidine deaminase and DNA cytosine methyltransferase. The latter activity makes zebularine a promising antitumor agent that is hydrolytically stable, preferentially targets cancer cells, and shows activity both in vitro and in experimental animals, even after oral administration.

引用

页码：246 / 254

页数：9

共 27 条

[11]

GONZALEZZULUETA M, 1995, CANCER RES, V55, P4531

[12] NUCLEIC-ACID COMPONENTS AND THEIR ANALOGS .188. PREPARATION OF ACYL DERIVATIVES OF PYRIMIDIN-2-ONE NUCLEOSIDES BY SILYL VARIANT OF HILBERT-JOHNSON REACTION [J].

HOLY, A .

COLLECTION OF CZECHOSLOVAK CHEMICAL COMMUNICATIONS, 1977, 42 (03) :902-908

[13] PREPARATION OF ANALOGS OF CYTOSINE AND 2-PYRIMIDINONE NUCLEOSIDES AND THEIR EFFECT ON BACTERIAL (ESCHERICHIA-COLI A19) CYTIDINE AMINOHYDROLASE [J].

HOLY, A ;

LUDZISA, A ;

VOTRUBA, I ;

SEDIVA, K ;

PISCHEL, H .

COLLECTION OF CZECHOSLOVAK CHEMICAL COMMUNICATIONS, 1985, 50 (02) :393-417

[14]

IVANCEVICH JM, 1992, ACADEMY MANAGEMENT E, V6, P42

[15] The fundamental role of epigenetic events in cancer [J].

Jones, PA ;

Baylin, SB .

NATURE REVIEWS GENETICS, 2002, 3 (06) :415-428

[16] HHAL METHYLTRANSFERASE FLIPS ITS TARGET BASE OUT OF THE DNA HELIX [J].

KLIMASAUSKAS, S ;

KUMAR, S ;

ROBERTS, RJ ;

CHENG, XD .

CELL, 1994, 76 (02) :357-369

[17] POTENT INHIBITORS FOR THE DEAMINATION OF CYTOSINE-ARABINOSIDE AND 5-AZA-2'-DEOXYCYTIDINE BY HUMAN CYTIDINE DEAMINASE [J].

LALIBERTE, J ;

MARQUEZ, VE ;

MOMPARLER, RL .

CANCER CHEMOTHERAPY AND PHARMACOLOGY, 1992, 30 (01) :7-11

[18] CYCLOPENTENYLURIDINE AND CYCLOPENTENYLCYTIDINE ANALOGS AS INHIBITORS OF URIDINE-CYTIDINE KINASE [J].

LIM, MI ;

MOYER, JD ;

CYSYK, RL ;

MARQUEZ, VE .

JOURNAL OF MEDICINAL CHEMISTRY, 1984, 27 (12) :1536-1538

[19] Potent inhibition of HhaI DNA methylase by the aglycon of 2-(1H)-pyrimidinone riboside (Zebularine) at the G(C)under-barGC recognition domain [J].

Marquez, VE ;

Eritja, R ;

Kelley, JA ;

Vanbemmel, D ;

Christman, J .

THERAPEUTIC OLIGONUCLEOTIDES: ANTISENSE, RNAI, TRIPLE-HELIX, GENE REPAIR, ENHANCER DECOYS, CPG AND DNA CHIPS, 2003, 1002 :154-164

[20] INHIBITION OF CYTIDINE DEAMINASE BY 2-OXOPYRIMIDINE RIBOSIDE AND RELATED-COMPOUNDS [J].

MCCORMACK, JJ ;

MARQUEZ, VE ;

LIU, PS ;

VISTICA, DT ;

DRISCOLL, JS .

BIOCHEMICAL PHARMACOLOGY, 1980, 29 (05) :830-832

← 1 2 3 →