A Selective Galactose–Coumarin-Derived Galectin‑3 Inhibitor Demonstrates Involvement of Galectin-3-glycan Interactions in a Pulmonary Fibrosis Model

Synthesis of doubly 3-O-coumarylmethyl-substituted
thiodigalactosides from bis-3-O-propargyl-thiodigalactoside
resulted in highly selective and high affinity galectin-3 inhibitors.
Mutant studies, structural analysis, and molecular modeling revealed
that the coumaryl substituents stack onto arginine side chains. One
inhibitor displayed efficacy in a murine model of bleomycin-induced
lung fibrosis similar to that of a known nonselective galectin-1/galectin-3
inhibitor, which strongly suggests that blocking galectin-3 glycan
recognition is an important antifibrotic drug target.