Synthetic multimeric heptyl mannosides as potent antiadhesives of uropathogenic Escherichia coli.
Urinary tract infections caused by uropathogenic Escherichia coli presents a serious communal and nosocomial health problem initiated by bacterial adhesion to the bladder cells. E. coli expresses fimbriae with a mannose-binding adhesin, FimH, at the tip. Heptyl alpha-D-mannoside (HM) is a nanomolar inhibitor of this lectin, preventing adhesion of type 1-piliated E. coli and reducing bacteria levels in a murine cystitis model. Herein, we described the synthesis of multimeric heptyl-mannosides with valencies ranging from one to four by copper-catalyzed azide alkyne cycloaddition (CuAAC). Biological evaluation of the multivalent compounds revealed an increase in potency compared to HM. Inhibition of bladder cell binding highlighted a promising tetravalent derivative with inhibitory concentrations 6000- and 64-fold lower than mannose and HM respectively.
Gouin
Sébastien G
SG
Department of Chemistry, Laboratoire des Glucides UMR CNRS 6219, Institut de Chimie de Picardie, Université de Picardie Jules Verne, 33 Rue Saint Leu, 80039 Amiens Cedex, France. sebastien.gouin@u-picardie.fr
Wellens
Adinda
A
Bouckaert
Julie
J
Kovensky
José
J