Glycoclusters presenting lactose on calix[4]arene cores display trypanocidal activity

A new series of water-soluble tetravalent glycoclusters incorporating β-lactosyl residues attached to a central calix[4]arene core was synthesised using azide-alkyne Cu(I)-catalysed cycloaddition ('click chemistry'). Carbohydrate moieties were attached either to the upper or lower rim of rigid cone-shaped or partial cone macrocycles via 14-21 atom spacer arms. The glycoclusters with a C4-symmetrical arrangement of β-lactosyl residues showed trypanocidal activity, with one of them showing comparable activity to established anti-trypanosomal drug benznidazole in in vitro anti-parasite assays.