Rational design of inhibitors of VirA-VirG two-component signal transduction

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:17

Article

Maresh, Justin ; Zhang, Jin ; Tzeng, Yih-Ling ; Goodman, Nora A. ; Lynn, David G.

关键词: two-component signaling;    pathogenesis;    Agrobacterium;    virulence;    therapeutics;    benzoxazinone;   

DOI  :  10.1016/j.bmcl.2007.04.018

来源: Elsevier

【 摘 要 】

VirA-VirG two-component system regulates the vir (virulence) operon in response to specific host factors (xenognosins) in the plant pathogen Agrobacterium tumefaciens. Using whole cell assays, stable inhibitors inspired by the labile natural benzoxazinone inhibitor HDMBOA are developed. It is found that aromatic aldehydes represent a minimal structural unit for activity. In particular, 3-hydroxy-4,6-dimethoxy-3H-isobenzofuran-1-one (HDI) was found to have the highest activity, making it the most potent developed inhibitor of virulence gene expression in Agrobacterium. (c) 2007 Elsevier Ltd. All rights reserved.

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