title: Antiviral Activity of Synthetic Aminopyrrolic Carbohydrate Binding Agents: Targeting the Glycans of Viral gp120 to Inhibit HIV Entry.
abstract: The binding abilities of a set of structurally related aminopyrrolic synthetic receptors for mannosides, endowed with antimycotic activity against yeast and yeast-like pathogens bearing mannoproteins on their cell surface, have been investigated towards the highly mannosylated gp120 and gp41 glycoproteins of the HIV envelope. A pronounced binding interaction with both glycoproteins was observed by SPR for most of the investigated compounds. Comparison of their binding properties towards the glycoproteins with their binding affinities toward mannosides revealed a direct correlation, supporting their role as carbohydrate binding agents (CBAs). Cytostatic activity studies revealed antiproliferative activity dependent on the nature and the structure of compounds. Antiviral activity studies against a broad panel of DNA and RNA viruses showed inhibitory effect against HIV infection of the T-lymphocyte CEM cell line for two compounds, suggesting antiviral activity similar to other CBAs, such as the nonpeptidic pradimicin antibiotics.
authors.affiliation: Dipartimento di Chimica, Università di Firenze, Polo Scientifico e Tecnologico, 50019 Sesto Fiorentino, Firenze (Italy). oscar.francesconi@unifi.it.
authors.forename: Oscar
authors.initials: O
authors.lastname: Francesconi
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.affiliation: Dipartimento di Chimica, Università di Firenze, Polo Scientifico e Tecnologico, 50019 Sesto Fiorentino, Firenze (Italy).
authors.forename: Gabriele
authors.initials: G
authors.lastname: Gabrielli
authors.affiliation: Dipartimento di Chimica, Università di Firenze, Polo Scientifico e Tecnologico, 50019 Sesto Fiorentino, Firenze (Italy).
authors.forename: Irene
authors.initials: I
authors.lastname: De Simone
authors.affiliation: Rega Institute for Medical Research, KU Leuven, 3000 Leuven (Belgium).
authors.forename: Sam
authors.initials: S
authors.lastname: Noppen
authors.affiliation: Rega Institute for Medical Research, KU Leuven, 3000 Leuven (Belgium).
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.affiliation: Rega Institute for Medical Research, KU Leuven, 3000 Leuven (Belgium).
authors.forename: Sandra
authors.initials: S
authors.lastname: Liekens
authors.affiliation: Istituto di Metodologie Chimiche (IMC), Consiglio Nazionale delle Ricerche (CNR), Dipartimento di Chimica, Polo Scientifico e Tecnologico, 50019 Sesto Fiorentino, Firenze (Italy).
authors.forename: Stefano
authors.initials: S
authors.lastname: Roelens
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D050260:Carbohydrate Metabolism / Q000187:drug effects; D002241:Carbohydrates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008362:Mannosides / Q000737:chemistry* / Q000494:pharmacology; D011134:Polysaccharides / Q000737:chemistry* / Q000378:metabolism
chemical_list: D019380:Anti-HIV Agents; D002241:Carbohydrates; D008362:Mannosides; D011134:Polysaccharides
keywords: HIV; antiviral agents; carbohydrate binding agents; medicinal chemistry; synthetic receptors