In vitro anti-Trypanosoma cruzi activity of ternary copper(II) complexes and in vivo evaluation of the most promising complex

Publication date: January 2019Source: Biomedicine & Pharmacotherapy, Volume 109Author(s): Drielly A. Paixão, Carla D. Lopes, Zumira A. Carneiro, Luana M. Sousa, Leticia P. de Oliveira, Norberto P. Lopes, Marcos Pivatto, Joana Darc S. Chaves, Mauro V. de Almeida, Javier Ellena, Mariete B. Moreira, Adelino V.G. Netto, Ronaldo J. de Oliveira, Silvana Guilardi, Sérgio de Albuquerque, Wendell GuerraAbstractIn 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)(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 103–104 M–1, with [C...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research