Structure-activity relationships among guanine-quadruplex telomerase inhibitors

被引：72

作者：

Neidle, S ^{[1
]}

Harrison, RJ ^{[1
]}

Reszka, AP ^{[1
]}

Read, MA ^{[1
]}

机构：

[1] Inst Canc Res, Chester Beatty Labs, CRC, Biomol Struct Unit, London SW3 6JB, England

来源：

PHARMACOLOGY & THERAPEUTICS | 2000年 / 85卷 / 03期

关键词：

telomerase; inhibitors; quadruplex; molecular modelling;

D O I：

10.1016/S0163-7258(99)00065-0

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The ribonucleoprotein telomerase is responsible for maintaining the length of telomeric ends of chromosomes in tumour cells. It is activated in over 85% of the tumour cells, and is emerging as a major target for cancer chemotherapy. A range of molecules containing tricyclic and tetracyclic aromatic chromophores has been shown to inhibit the telomerase enzyme system at the micromolar level. There is evidence that they do so via stabilisation of a guanine-quadruplex structure, which provides a stop signal for further telomere elongation. The known structure-activity relationships for these compounds are summarised, and pointers for the development of future molecules with enhanced selectivity are described. (C) 2000 Elsevier Science Inc. All rights reserved.

引用

页码：133 / 139

页数：7

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