Synthesis and biological evaluation of mannosyl triazoles and varying the nature of substituents on the terminal phthalimido moiety in the aglycone backbone

Abstract

In the present study, a facile synthesis of six monovalent α-d-mannoside ligands terminated with phthalimido moiety by Cu(I) catalyzed azide-alkyne cycloaddition reaction (CuAAC) has been achieved. All synthesized ligands were tested for their inhibitory activities against E. coli FimH adhesion using hemagglutination inhibition (HAI) assay and showed inhibitory activity in the range of HAI = 4.8–23.5 µM comparing with 2-azidoethyl α-d-mannopyranoside 17 as the standard ligand (HAI = 135 µM). Among them, ligand 21 (R = NO2), displayed the best activity (HAI = 4.8 µM) which was approximately 28 times more potent than the reference ligand 17. Thus confirming the beneficial effect of lipophilic interactions between the aromatic aglycone and the tyrosine gate of FimH. We feel that our lead ligand will be a good platform for identification of more potent FimH inhibitors.

Keywords

• 1,2,3-triazole
• Hemagglutination
• Mannoconjugate
• Urinary tract infection