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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Binding of triazole-linked galactosyl arylsulfonamides to galectin-3 affects Trypanosoma cruzi cell invasion

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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
[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

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 type: Research Grants - Young Investigators Grants