Publication: In vitro anti-Trypanosoma cruzi activity of ternary copper(II) complexes and in vivo evaluation of the most promising complex
Loading...
Date
Advisor
Coadvisor
Graduate program
Undergraduate course
Journal Title
Journal ISSN
Volume Title
Publisher
Type
Article
Access right
Acesso aberto
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 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.
Description
Keywords
Chagas disease, Cu(II) complexes, DNA binding, Hydrazides, Molecular docking, T. cruzi
Language
English
Citation
Biomedicine and Pharmacotherapy, v. 109, p. 157-166.
