Paixão, Drielly A.Lopes, Carla D.Carneiro, Zumira A.Sousa, Luana M.de Oliveira, Leticia P.Lopes, Norberto P.Pivatto, MarcosChaves, Joana Darc S.de Almeida, Mauro V.Ellena, JavierMoreira, Mariete B. [UNESP]Netto, Adelino V.G. [UNESP]de Oliveira, Ronaldo J.Guilardi, Silvanade Albuquerque, SérgioGuerra, Wendell2019-10-062019-10-062019-01-01Biomedicine and Pharmacotherapy, v. 109, p. 157-166.1950-60070753-3322http://hdl.handle.net/11449/189671In 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 α-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)(ClO 4 ) 2 ], exhibited a higher selectivity index than that recommended for preclinical studies. Considering this observation, complex [Cu(4-MH)(dmb)(ClO 4 ) 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 K b values in the range of 10 3 –10 4 M –1 , with [Cu(4-MH)(dmb)(ClO 4 ) 2 ] showing the highest K b value (1.45 × 10 4 M –1 ). Molecular docking simulations predicted that [Cu(4-MH)(dmb)(ClO 4 ) 2 ] binds in the minor groove of the double helix of ct-DNA and forms one hydrogen bond.157-166engChagas diseaseCu(II) complexesDNA bindingHydrazidesMolecular dockingT. cruziArtigo10.1016/j.biopha.2018.10.057Acesso aberto2-s2.0-85055895361