Synthesis of sialoclusters appended to calix[4]arene platforms via multiple azide-alkyne cycloaddition. New inhibitors of hemagglutination and cytopathic effect mediated by BK and influenza A viruses.
Tetra- and octavalent sialoside clusters were prepared in good yields exploiting for the first time the multiple copper-catalyzed cycloaddition of a propargyl thiosialoside with calix[4]arene polyazides. The cycloadducts featured the hydrolytically stable carbon-sulfur bond at the anomeric position and the 1,4-disubstituted triazole ring as the spacer between the sialic acid moieties and the platform. It was demonstrated that these unnatural motifs did not hamper the desired biological activity of the sialoclusters. In fact, they were able to inhibit, at submillimolar concentrations, the hemagglutination and the viral infectivity mediated both by BK and influenza A viruses.
Marra
Alberto
A
Dipartimento di Chimica, Laboratorio di Chimica Organica, Università di Ferrara, Via Borsari 46, I-44100, Ferrara, Italy.
Moni
Lisa
L
Pazzi
Daniele
D
Corallini
Alfredo
A
Bridi
Deborah
D
Dondoni
Alessandro
A
D000480:Alkynes / Q000737:chemistry; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001386:Azides / Q000737:chemistry; D001739:BK Virus / Q000187:drug effects; D047250:Calixarenes / Q000737:chemistry*; D002384:Catalysis; D002522:Chlorocebus aethiops; D003300:Copper / Q000737:chemistry; D003500:Cyclization; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects*; D006027:Glycosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006385:Hemagglutination Inhibition Tests; D006387:Hemagglutination, Viral / Q000187:drug effects*; D009980:Influenza A virus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D019158:N-Acetylneuraminic Acid / Q000737:chemistry; D010636:Phenols / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014709:Vero Cells
D000480:Alkynes; D000998:Antiviral Agents; D001386:Azides; D006027:Glycosides; D010636:Phenols; D013438:Sulfhydryl Compounds; C121325:calix(4)arene; D047250:Calixarenes; D003300:Copper; D019158:N-Acetylneuraminic Acid