Abstract

In vitro anti-Trypanosoma cruzi activity of ternary copper(II) complexes and in vivo evaluation of the most promising complex.
PAIXÃO, Drielly A.; LOPES, Carla D.; CARNEIRO, Zumira A.; SOUSA, Luana M.; OLIVEIRA, Leticia P.; LOPES, Norberto Peporine; PIVATTO, Marcos; CHAVES, Joana Darc S.; ALMEIDA, Mauro V.; ELLENA, Javier; MOREIRA, Mariete B.; V. G. NETTO, Adelino; OLIVEIRA, Ronaldo J.; GUILARDI, Silvana; ALBUQUERQUE, Sérgio de; GUERRA, Wendell.
Abstract: In order to improve the previously observed antichagasic activity of Cu(II) complexes containing 2-chlorobenzhydrazide (2-CH), we report herein the synthesis and anti-Trypanosoma cruzi activity of novel copper complexes containing 2-methoxybenzhydrazide (2-MH), 4-methoxybenzhydrazide (4-MH) and three a-diimine ligands, namely, 1,10-phenanthroline (phen), 2,2-bipyridine (bipy) and 4-4'-dimethoxy-2-2'-bipyridine (dmb). Two of these complexes showed higher in vitro anti-Trypanosoma cruzi activity when compared to benznidazole, the main drug used in Chagas disease treatment. One of them, the copper complex with 4-MH and dmb, [Cu(4- MH)(dmb)(ClO4)2], exhibited a higher selectivity index than that recommended for preclinical studies. Considering this observation, complex [Cu(4-MH)(dmb)(ClO4)2] was selected for preliminary in vivo assays, which verified that this compound was able to reduce parasitemia by 64% at the peak of infection. Further investigations were performed on all compounds. The Cu(II) complexes bind to ct-DNA with Kb values in the range of 10^3-10^4 M-1, with [Cu(4-MH)(dmb)(ClO4)2] showing the highest Kb value (1.45×10^4 M-1). Molecular docking simulations predicted that [Cu(4-MH)(dmb)(ClO4)2] binds in the minor groove of the double helix of ct- DNA and forms one hydrogen bond.
Biomedicine and Pharmacotherapy
v. 109, p. 157-166 - Ano: 2019
Fator de Impacto: 3,457
http://dx.doi.org/10.1016/j.biopha.2018.10.057
    @article={002911487,author = {PAIXÃO, Drielly A.; LOPES, Carla D.; CARNEIRO, Zumira A.; SOUSA, Luana M.; OLIVEIRA, Leticia P.; LOPES, Norberto Peporine; PIVATTO, Marcos; CHAVES, Joana Darc S.; ALMEIDA, Mauro V.; ELLENA, Javier; MOREIRA, Mariete B.; V. G. NETTO, Adelino; OLIVEIRA, Ronaldo J.; GUILARDI, Silvana; ALBUQUERQUE, Sérgio de; GUERRA, Wendell.},title={In vitro anti-Trypanosoma cruzi activity of ternary copper(II) complexes and in vivo evaluation of the most promising complex},journal={Biomedicine and Pharmacotherapy},note={v. 109, p. 157-166},year={2019}}

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