Antiadhesive glycoconjugate metal complexes targeting pathogens Pseudomonas aeruginosa and Candida albicans

Glycoconjugates are known to interact with carbohydrate-binding proteins involved in adhesion by pathogens, and offer opportunities to design antimicrobial agents. Metal complexes with Eu(III), Ni(II) and Zn(II) were prepared from glycoconjugate ligand 1Gal, which binds to P. aeruginosa's lectin LecA (Kd 9.6 ± 0.7 μM). In vitro anti-adhesive activity of these compounds was evaluated for both P. aeruginosa and C. albicans. Choice of metal ion played a crucial role in modulating anti-adhesive activity, with Eu(III) complexes most effective: [Eu·(1Gal)(H2O)6](CF3SO3)3 inhibits 60% biofilm formation by P. aeruginosa and [Eu·(1Gal)3](CF3SO3)3 inhibits 62% of C. albicans adhesion to buccal epithelial cells (both at 0.1 mM). The results presented demonstrate the potential for metal coordination to significantly enhance biological activity of glycoconjugates, surpassing the effect of the ligand's modest lectin-binding affinity alone.