title: Design, synthesis and the effect of 1,2,3-triazole sialylmimetic neoglycoconjugates on Trypanosoma cruzi and its cell surface trans-sialidase.
abstract: This work describes the synthesis of a series of sialylmimetic neoglycoconjugates represented by 1,4-disubstituted 1,2,3-triazole-sialic acid derivatives containing galactose modified at either C-1 or C-6 positions, glucose or gulose at C-3 position, and by the amino acid derivative 1,2,3-triazole fused threonine-3-O-galactose as potential TcTS inhibitors and anti-trypanosomal agents. This series was obtained by Cu(I)-catalysed azide-alkyne cycloaddition reaction ('click chemistry') between the azido-functionalized sugars 1-N(3)-Gal (commercial), 6-N(3)-Gal, 3-N(3)-Glc and 3-N(3)-Gul with the corresponding alkyne-based 2-propynyl-sialic acid, as well as by click chemistry reaction between the amino acid N(3)-ThrOBn with 3-O-propynyl-GalOMe. The 1,2,3-triazole linked sialic acid-6-O-galactose and the sialic acid-galactopyranoside showed high Trypanosoma cruzitrans-sialidase (TcTS) inhibitory activity at 1.0mM (approx. 90%), whilst only the former displayed relevant trypanocidal activity (IC(50) 260μM). These results highlight the 1,2,3-triazole linked sialic acid-6-O-galactose as a prototype for further design of new neoglycoconjugates against Chagas' disease.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP, Av. Café S/N, CEP 14040-903, Ribeirão Preto, SP, Brazil.
authors.forename: Vanessa L
authors.initials: VL
authors.lastname: Campo
authors.forename: Renata
authors.initials: R
authors.lastname: Sesti-Costa
authors.forename: Zumira A
authors.initials: ZA
authors.lastname: Carneiro
authors.forename: João S
authors.initials: JS
authors.lastname: Silva
authors.forename: Sergio
authors.initials: S
authors.lastname: Schenkman
authors.forename: Ivone
authors.initials: I
authors.lastname: Carvalho
mesh_terms: D000480:Alkynes / Q000737:chemistry; D000977:Antiparasitic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001386:Azides / Q000737:chemistry; D002384:Catalysis; D057930:Click Chemistry; D003300:Copper / Q000737:chemistry; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006001:Glycoconjugates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006023:Glycoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012794:Sialic Acids / Q000737:chemistry; D014230:Triazoles / Q000737:chemistry*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000201:enzymology
chemical_list: D000480:Alkynes; D000977:Antiparasitic Agents; D001386:Azides; D004791:Enzyme Inhibitors; D006001:Glycoconjugates; D006023:Glycoproteins; D012794:Sialic Acids; D014230:Triazoles; D003300:Copper; C069715:trans-sialidase; D009439:Neuraminidase