Non‐Carbohydrate Glycomimetics as Inhibitors of Calcium(II)‐Binding Lectins

Because of the antimicrobial resistance crisis, lectins are considered novel drug targets. Pseudomonas aeruginosa utilizes LecA and LecB in infection process. Inhibition both with carbohydrate-derived molecules can reduce biofilm formation to restore susceptibility. Here, we focused on non-carbohydrate inhibitors for explore new avenues lectin inhibition. From a screening cascade obtained one experimentally confirmed hit, catechol, belonging well-known PAINS compounds. Rigorous analyses validated electron-deficient catechols as millimolar inhibitors. The first co-crystal structure inhibitor complex bacterial clearly demonstrates catechol mimicking binding natural glycosides LecA. Importantly, 3 is ligand that binds mammalian calcium(II)-binding lectins, giving rise this fundamentally class glycomimetics.