Inhibitors of type III secretion in Yersinia: design, synthesis and multivariate QSAR of 2-sulfonamino-benzanilides
2007 (English)In: Bioorganic & Medicinal Chemistry, ISSN 0968-0896, E-ISSN 1464-3391, Vol. 15, no 22, 6994-7011 p.Article in journal (Other academic) Published
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 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.
Place, publisher, year, edition, pages
Elsevier Ltd , 2007. Vol. 15, no 22, 6994-7011 p.
Type III secretion, Yersinia, Virulence, Inhibitors, Statistical molecular design: multivariate QSAR
IdentifiersURN: urn:nbn:se:umu:diva-5559DOI: 10.1016/j.bmc.2007.07.047OAI: oai:DiVA.org:umu-5559DiVA: diva2:145110
Available online 22 August 2007