title: 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.
authors.affiliation: Dipartimento di Chimica, Università di Firenze, Polo Scientifico e Tecnologico, 50019 Sesto Fiorentino, Firenze, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Nativi
authors.forename: Oscar
authors.initials: O
authors.lastname: Francesconi
authors.forename: Gabriele
authors.initials: G
authors.lastname: Gabrielli
authors.forename: Irene
authors.initials: I
authors.lastname: De Simone
authors.forename: Benedetta
authors.initials: B
authors.lastname: Turchetti
authors.forename: Tommaso
authors.initials: T
authors.lastname: Mello
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Di Cesare Mannelli
authors.forename: Carla
authors.initials: C
authors.lastname: Ghelardini
authors.forename: Pietro
authors.initials: P
authors.lastname: Buzzini
authors.forename: Stefano
authors.initials: S
authors.lastname: Roelens
mesh_terms: D000666:Amphotericin B / Q000737:chemistry* / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology*; D002241:Carbohydrates / Q000737:chemistry*; D003593:Cytoplasm / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008362:Mannosides / Q000737:chemistry*; D015394:Molecular Structure; D009005:Monosaccharides / Q000737:chemistry*; D010539:Permeability; D011758:Pyrroles / Q000737:chemistry*; D013329:Structure-Activity Relationship; D015003:Yeasts / Q000737:chemistry* / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D002241:Carbohydrates; D008362:Mannosides; D009005:Monosaccharides; D011758:Pyrroles; D000666:Amphotericin B