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ID: ALA1137500

Journal: Bioorg Med Chem

Title: Inhibitors of type III secretion in Yersinia: design, synthesis and multivariate QSAR of 2-arylsulfonylamino-benzanilides.

Authors: Kauppi AM, Andersson CD, Norberg HA, Sundin C, Linusson A, Elofsson M.

Abstract: 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.

CiteXplore: 17851084

DOI: 10.1016/j.bmc.2007.07.047