| Full text | |
| Author(s): Show less - |
Marchiori, Marcelo Fiori
[1]
;
Riul, Thalita B.
[1]
;
Bortot, Leandro Oliveira
[1]
;
Andrade, Peterson
[1]
;
Junqueira, Getulio G.
[1]
;
Foca, Giuseppina
[2]
;
Doti, Nunzianna
[2]
;
Ruvo, Menotti
[2]
;
Dias-Baruffi, Marcelo
[1]
;
Carvalho, Ivone
[1]
;
Campo, Vanessa Leiria
[1]
Total Authors: 11
|
| Affiliation: | [1] Univ Sao Paulo, Fac Pharmaceut Sci Ribeirao Preto, Av Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil
[2] CNR, Ist Biostrutture & Bioimmagini, Via Mezzocannone 16, I-80134 Naples - Italy
Total Affiliations: 2
|
| Document type: | Journal article |
| Source: | Bioorganic & Medicinal Chemistry; v. 25, n. 21, p. 6049-6059, NOV 1 2017. |
| Web of Science Citations: | 3 |
| Abstract | |
The synthesis of the O-3 triazole-linked galactosyl arylsulfonamides 1-7 as potential inhibitors of Trypanosoma cruzi cell invasion is described. These target compounds were synthesized by Cu(I)-catalysed azide-alkyne cycloaddition reaction ('click chemistry') between different azide arylsulfonamides and the alkyne-based sugar 3-O-propynyl-bGalOMe. Inhibition assays of T. cruzi cell invasion with compounds 1-7 showed reduced values of infection index (similar to 20) for compounds 3 and 5, bearing the corresponding 5-methylisoxazole and 2,4-dimethoxypyrimidine groups, which also presented higher binding affinities to galectin-3 (EC50 17-18 mu M) in Corning Epic label-free assays. In agreement with experimental results, the assessment of the theoretical binding of compounds 1-7 to galectin-3 by MM/PBSA method displayed higher affinities for compounds 3 (- 9.7 kcal/mol) and 5 (- 11.1 kcal/mol). Overall, these achievements highlight compounds 3 and 5 as potential T. cruzi cell invasion blockers by means of a galectin-3 binding-related mechanism, revealing galectin-3 as an important host target for design of novel anti-trypanosomal agents. (C) 2017 Elsevier Ltd. All rights reserved. (AU) | |
| FAPESP's process: | 12/19390-0 - Development of mucin glycoconjugates with diagnostic and therapeutic applications in muscular dystrophies and cancer |
| Grantee: | Vanessa Leiria Campo |
| Support Opportunities: | Research Grants - Young Investigators Grants |