Silver and copper-benznidazole derivatives as potential antiparasitic metallodrugs: Synthesis, characterization, and biological evaluation

Author(s)

de Souza, Cassiano Cunha ; de Azevedo-Franca, Jose Aleixo ; Barrias, Emile ; Cavalcante, Stephany C. F. ; Vieira, Eduardo Guimaraes ; Ferreira, Ana Maria Da Costa ; de Souza, Wanderley ; Navarro, Maribel

• Document type: Journal article
• Source: Journal of Inorganic Biochemistry; v. 239, p. 12-pg., 2022-12-20.

Abstract

Currently the only drug available to treat Chagas disease in Brazil is benznidazole (BZN). Therefore, there is an urgent need to discover and develop new anti-Trypanosoma cruzi candidates. In our continuous effort to enhance clinical antiparasitic drugs using synergistic strategy, BZN was coordinated to silver and copper ions to enhance its effectiveness to treat that illness. In this work, the syntheses of four novel metal-BZN complexes, [Ag(BZN)2] NO3 & sdot;H2O (1), [CuCl2(BZN)(H2O)]& sdot;1/2CH3CN (2), [Ag(PPh3)2(BZN)2]NO3 & sdot;H2O (3), and [Cu(PPh3)2(BNZ)2] NO3 & sdot;2H2O (4), and their characterization using multiple analytical and spectroscopic techniques such as Infrared (FTIR), Nuclear Magnetic Resonance (1H, 13C, 31P), UV-Visible (UV-Vis), Electron Paramagnetic Resonance (EPR), conductivity and elemental analysis are described. IC50 (Half-maximal inhibitory concentration) values of Ag-BZN compounds are about five to ten times lower than benznidazole itself in both proliferation stages of the parasite (epimastigotes and amastigotes). The cytotoxicity of both compounds in human cells (fibroblasts and hepatocytes) are comparable to BZN, indicating that Ag-BZN complexes can be more selective than BZN. (AU)

• FAPESP's process: 16/16735-8 - Imobilization of potential metallopharmaceuticals in inorganic and organic matrices for modified delivery
• Grantee: Eduardo Guimarães Vieira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC