Chagas’ disease,also known as American trypanosomiasis, is one of the most devastating tropical disease and it is caused by the protozoanTrypanosoma cruzi.[1]Several therapeutic targets are used in the study of Chagas’ disease, specially the regulatory surface enzyme called trans-sialidase(TcTS).TheTcTS is responsible for the transference of sialic acids from host cells to terminal β-galactose molecules present on its glycoprotein surface. As a result, TcTS plays a key role in the recognition and invasion of host cells in the infection process.[2]Despite the importance of this enzyme in the pathogenesis of Chagas’ disease, the discover of potent inhibitor is still a challenge.
Recently, sulfonamide and galactose derivatives was shown to be potent inhibitors TcTS[3,4], andthereby, we envisaged the synthesis of galactosyl-triazole-benzenesulfonamides derivatives aiming inhibition of TcTS.Thus, the developed work allowed the synthesis of compounds1-7in few steps and good yields, usingcopper-catalyzed azide–alkyne cycloadditionreactions (CuAAC). Furthermore, these compounds were tested towards TcTS by fluorimetric assay, which showed moderate inhibition (~40% at 1mM) for compounds1-6, and high inhibition (~80% at 1mM) for compound7. Ongoing studies based on anti-trypanosomal and cytotoxicity activities will be presented.
1. M. Sanchez-Moreno, A. M Sanz, F. Gomez-Contreras, P. Navarro, C. Marin, I. Ramirez-Macias, M. J. Rosales, F. Olmo, I. Garcia-Aranda, L. Campayo, C. Cano, F. Arrebola, M. J. R Yunta,Journal of Medicinal Chemistry,2011, 54, 970-979.
2. I. Carvalho, P. Andrade, V. L. Campo, P. M. M. Guedes, R. Sesti-Costa,J. S. Silva, S. Schenkman, S. Dedola, L. Hill, M. Rejzek, S. A. Nepogodiev, R. A. Field,Bioorganic Medicinal Chemistry,2010, 18, 2412-2427.
3. Das, J.; Patil, S. N.; Awasthi, R.; Narasimhulu, C. P.; Trehan, S.Synthesis.2005,11, 1801.
4. Campo,V. L.; Sesti-Costa, R.; Carneiro, Z. A.; Silva, J.S.; Schenkman, S.; Carvalho, I.Bioorganic & Medicinal Chemistry.2012,20. 145.
