Aminopyrrolic Synthetic Receptors for Monosaccharides: A Class of Carbohydrate‐Binding Agents Endowed with Antibiotic Activity versus Pathogenic Yeasts

Abstract

The biological activity of a set of structurally related aminopyrrolic synthetic receptors for monosaccharides has been tested versus yeast and yeast-like microorganisms and compared to their binding affinity toward mannosides. Antibiotic activity comparable to that of well-known polyene (amphotericin B) or azole (ketoconazole) drugs has been found for some members of the family, along with a general correlation with binding abilities. A systematic structure-activity-affinity investigation shed light on the structural and functional requirements necessary for antibiotic activity and identified the tripodal compound 1 as the most potent compound of the set. Together with toxicity tests and inhibitor localization experiments performed through fluorescence microscopy, these studies led to the characterization of a new class of carbohydrate binding agents possessing antibiotic activity, in which pyrrolic groups precisely structured on a tripodal architecture appear to be responsible for permeability through the cell wall of pathogens, as well as for antibiotic activity inside the cytoplasm.