Molecular modelling and cytotoxicity of substituted anthraquinones as inhibitors of human telomerase

被引：55

作者：

Cairns, D ^{[1
]}

Michalitsi, E

Jenkins, TC

Mackay, SP

机构：

[1] Univ Sunderland, Inst Pharm & Chem, Sunderland SR1 3SD, England

[2] Univ Bradford, YCR Lab Drug Design, Bradford BD7 1DP, W Yorkshire, England

[3] Univ Strathclyde, Strathclyde Inst Biomed Sci, Glasgow G4 0NR, Lanark, Scotland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2002年 / 10卷 / 03期

关键词：

D O I：

10.1016/S0968-0896(01)00337-6

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：

Molecular modelling has been carried out for a number of amine-functionalised anthraquinone derivatives to determine their extent of binding to G-tetraplex DNA and their ability to inhibit the enzymes telomerase and Tay polymerase. The results are compared to data obtained from a modified TRAP assay and show good correlation between the two methods. The findings suggest that anthraquinone derivatives of this type inhibit telomerase by stabilisation of four-stranded tetraplex structures associated with guanine-rich telomeric DNA regions. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：803 / 807

页数：5

共 27 条

[1] TELOMERE LENGTH PREDICTS REPLICATIVE CAPACITY OF HUMAN FIBROBLASTS [J].

ALLSOPP, RC ;

VAZIRI, H ;

PATTERSON, C ;

GOLDSTEIN, S ;

YOUNGLAI, EV ;

FUTCHER, AB ;

GREIDER, CW ;

HARLEY, CB .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (21) :10114-10118

[2] EVIDENCE FOR A CRITICAL TELOMERE LENGTH IN SENESCENT HUMAN FIBROBLASTS [J].

ALLSOPP, RC ;

HARLEY, CB .

EXPERIMENTAL CELL RESEARCH, 1995, 219 (01) :130-136

[3] ATOMIC CHARGES DERIVED FROM SEMIEMPIRICAL METHODS [J].

BESLER, BH ;

MERZ, KM ;

KOLLMAN, PA .

JOURNAL OF COMPUTATIONAL CHEMISTRY, 1990, 11 (04) :431-439

[4] STRUCTURE AND FUNCTION OF TELOMERES [J].

BLACKBURN, EH .

NATURE, 1991, 350 (6319) :569-573

[5]

CAIRNS D, 2001, IN PRESS CURR PHARM

[6]

CHENG JF, 1989, NUCLEIC ACIDS RES, V17, P61109

[7] Effect of DNA secondary structure on human telomerase activity [J].

Fletcher, TM ;

Sun, DK ;

Salazar, M ;

Hurley, LH .

BIOCHEMISTRY, 1998, 37 (16) :5536-5541

[8]

Gibson V., 1999, Pharmacy and Pharmacology Communications, V5, P669

[9]

GIBSON V, 1996, PHARM SCI, V2, P545

[10] TELOMERES SHORTEN DURING AGING OF HUMAN FIBROBLASTS [J].

HARLEY, CB ;

FUTCHER, AB ;

GREIDER, CW .

NATURE, 1990, 345 (6274) :458-460

← 1 2 3 →