Sulfonamide-metal complexes endowed with potent anti-Trypanosoma cruzi activity

Journal of Enzyme Inhibition and Medicinal Chemistry Volume: 29 Issue: 2 Pages: 230-236 Published: 2014

Calculated molecular structure of complexes C9–12.

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Writers: Zahid H. Chohan, Marcelo Zaldini Hernandes, Fabricio R. Sensato, Diogo Rodrigo Magalhaes Moreira, Valéria Rego Alves Pereira, Juliana Kelle de Andrade Lemoine Neves, Andresa Pereira de Oliveira, Beatriz Coutinho de Oliveira & Ana Cristina Lima Leite

Keywords: CobaltcopperDFTmetal complexesprodrugssulfonamidesTrypanosoma cruzi

Abstract: In this article, we describe that mononuclear complexes composed of (5-chloro-2-hydroxybenzylidene) aminobenzenesulfonamides (L1–3) of general formula (L2(M)2H2O, where M is Co, Cu, Zn, Ni or Mn) reduced epimastigote proliferation and were found cidal for trypomastigotes of Trypanosoma cruzi Y strain. Complexes C5 and C11 have IC50 of 2.7 ± 0.27 and 4.8 ± 0.47 µM, respectively, for trypomastigotes, when the positive control Nifurtimox, which is also an approved drug for Chagas disease, showed IC50 of 2.7 ± 0.25 µM. We tested whether these complexes inhibit the enzyme T. cruzi trypanothione reductase or acting as DNA binders. While none of these complexes inhibited trypanothione reductase, we observed some degree of DNA binding, albeit less pronounced than observed for cisplatin in this assay. Unfortunately, most of these complexes were also toxic for mouse splenocytes. Along with the present studies, we discuss a number of interesting structure–activity relationships and chemical features for these metal complexes, including computational calculations.

Rose Portasio
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Assessora Administrativa no LIEC - IQ/Unesp