In:
Pure and Applied Chemistry, Walter de Gruyter GmbH, Vol. 91, No. 7 ( 2019-07-26), p. 1191-1207
Abstract:
The multivalent effect of carbohydrates (glycoclusters) has been explored to study important biological targets and processes involving Trypanosoma cruzi ( T. cruzi ) infection. Likewise, CuAAC cycloaddition reactions (click chemistry) have been applied as useful strategy in the discovery of bioactive molecules. Hence, we describe the synthesis of 1,2,3-triazole-based tetravalent homoglycoclusters ( 1–3 ) and heteroglycoclusters ( 4 and 5 ) of d -galactopyranose (C-1 and C-6 positions) and sialic acid (C-2 position) to assess their potential to inhibit T. cruzi cell invasion and also its cell surface trans- sialidase (TcTS). The target compounds were synthesised in good yields (52–75 %) via click chemistry by coupling azidosugars galactopyranose and sialic acid with alkynylated pentaerythritol or tris(hydroxymethyl)-aminomethane (TRIS) scaffolds. T. cruzi cell invasion inhibition assays showed expressive low parasite infection index values (5.3–6.8) for most compounds. However, most glycoclusters proved to be weak TcTS inhibitors at 1 mM ( 〈 17 %), except the tetravalent sialic acid 3 (99 % at 1 mM, IC 50 450 μM). Therefore, we assume that T. cruzi cell invasion blockage is not due to TcTS inhibition by itself, but rather by other mechanisms involved in this process. In addition, all glycoclusters were not cytotoxic and had significant trypanocidal activity upon parasite survival of amastigote forms.
Type of Medium:
Online Resource
ISSN:
1365-3075
,
0033-4545
DOI:
10.1515/pac-2019-0216
Language:
English
Publisher:
Walter de Gruyter GmbH
Publication Date:
2019
detail.hit.zdb_id:
2022101-0
Permalink