Inhibitors of type III secretion in Yersinia: Design, synthesis and multivariate QSAR of 2-arylsulfonylamino-benzanilides
- 作者：Anna M. Kauppi ; C. David Andersson ; Henrik A. Norberg ; Charlotta Sundin ; Anna Linusson ; Mikael Elofsson
- 关键词：Type III secretion ; Yersinia ; Virulence ; Inhibitors ; Statistical molecular design ; multivariate QSAR
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：2007
- 期刊代码：9_09680896
- 类别：ch
- 出版时间：15 November 2007
- 卷：15
- 期：22
- 页码：6994-7011
- 文件大小：654 K
摘要
Compound 1, 2-(benzo[1,2,5]thiadiazole-4-sulfonylamino)-5-chloro-N-(3,4-dichloro-phenyl)-benzamide, was identified as a putative type III secretion inhibitor in Yersinia, and the compound thus has a potential to be used to prevent or treat bacterial infections. A set of seven analogues was synthesized and evaluated in a type III secretion dependent reporter-gene assay with viable bacterial to give basic SAR. A second set of 19 compounds was obtained by statistical molecular design in the building block and product space and by subsequent synthesis. Evaluation in the reporter-gene assay showed that the compounds ranged from non-active to compounds more potent than 1. Based on the data multivariate QSAR models were established and the final Hi-PLS model showed good correlation between experimentally determined%inhibition and the calculated%inhibition of the reporter-gene signal.