Optimization of anti-proliferative activity using a screening approach with a series of bis-heterocyclic G-quadruplex ligands

被引：16

作者：

Ohnmacht, Stephan A. ^{[1
]}

Ciancimino, Cristina ^{[1
]}

Vignaroli, Giulia ^{[1
]}

Gunaratnam, Mekala ^{[1
]}

Neidle, Stephen ^{[1
]}

机构：

[1] UCL, UCL Sch Pharm, London WC1N 1AX, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 19期

关键词：

Quadruplex; Anti-proliferative; Phenotypic screening; Telomerase; Oxazoles; HIGHLY SELECTIVE LIGANDS; C-MYC; CRYSTAL-STRUCTURE; SMALL-MOLECULE; DNA; PROMOTER; SEQUENCE; TELOMERE; TARGETS; REGION;

D O I：

10.1016/j.bmcl.2013.07.057

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Using a phenotypic screening and SAR optimization approach, a phenyl-bis-oxazole derivative has been identified with anti-proliferative activity, optimized with the use of a panel of cancer cell lines. The lead compound was synthesized by means of a short and effective two-step synthesis using Pd-catalyzed direct arylation. The compound stabilizes several quadruplex DNA sequences including a human telomeric DNA and one from the promoter of the HSP90 gene, although the structure-activity relationships of the series are not obviously related to the quadruplex binding. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：5351 / 5355

页数：5

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