title: Inhibitors of type III secretion in Yersinia: design, synthesis and multivariate QSAR of 2-arylsulfonylamino-benzanilides.
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.
authors.affiliation: Department of Chemistry, Umeå University, SE-90187 Umeå, Sweden.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Kauppi
authors.forename: C David
authors.initials: CD
authors.lastname: Andersson
authors.forename: Henrik A
authors.initials: HA
authors.lastname: Norberg
authors.forename: Charlotta
authors.initials: C
authors.lastname: Sundin
authors.forename: Anna
authors.initials: A
authors.lastname: Linusson
authors.forename: Mikael
authors.initials: M
authors.lastname: Elofsson
mesh_terms: D000813:Anilides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015195:Drug Design; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D015999:Multivariate Analysis; D021281:Quantitative Structure-Activity Relationship; D013237:Stereoisomerism; D015011:Yersinia pseudotuberculosis / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism
chemical_list: D000813:Anilides; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C034595:benzanilide