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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:23

Article

Ohnmacht, Stephan A.¹  Ciancimino, Cristina¹  Vignaroli, Giulia¹  Gunaratnam, Mekala¹  Neidle, Stephen¹ 

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

关键词: Quadruplex;    Anti-proliferative;    Phenotypic screening;    Telomerase;    Oxazoles;   

DOI  :  10.1016/j.bmcl.2013.07.057

来源: Elsevier

【 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.

【 授权许可】

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