Cyto-genotoxic evaluation of novel anti-tubercular copper (II) complexes containing isoniazid-based ligands

Author(s)

Fregonezi, Nathalia Ferreira ^[1] ; de Souza, Fabiana Aparecida ^[1] ; Aleixo, Nadia Andrade ^[1] ; da Silva Gomes, Pietra Stefany ^[1] ; Silvestre, Rafaela Baldassari ^[1] ; De Grandis, Rone Aparecido ^{[1, 2]} ; da Silva, Patricia Bento ^[2] ; Pavan, Fernando Rogerio ^[2] ; Chorilli, Marlus ^[2] ; Resende, Flavia Aparecida ^[1]

Affiliation

^[1] UNIARA Univ Araraquara, Dept Biol Sci & Hlth, Araraquara 14801340, SP - Brazil

^[2] UNESP Sao Paulo State Univ, Fac Pharmaceut Sci Araraquara, Dept Biol Sci, Araraquara 14801902, SP - Brazil

• Document type: Journal article
• Source: REGULATORY TOXICOLOGY AND PHARMACOLOGY; v. 113, JUN 2020.
• Web of Science Citations: 0

Abstract

Considering the promising previous results of Cu (II) complexes with isoniazid active ligand against Mycobacterium tuberculosis, the main causative agent of tuberculosis, novel biological assays evaluating its toxicogenic potential were performed to ensure the safe use. The genotoxicity/mutagenicity of the complexes CuCl2(INH)(2)center dot H2O (I1), Cu(NCS)(2)(INH)(2)center dot 5H(2)O (I2) and Cu(NCO)(2)(INH)(2)center dot 4H(2)O (I3) was evaluated by the Comet, Micronucleus-cytome and Salmonella microsome (Ames test) assays. The cell viability using resazurin assay indicated that I1, I2 e I3 had moderate to low capacity to reduce the viability of colorectal cells (Caco-2), liver cells (HepG2), lung cells (GM 07492-A and A549) and endothelial cells (HU-VE-C). On genotoxicity/mutagenicity, I1 complex did not induce sizable levels of DNA damage in HepG2 cells (Comet assay), and gene (Ames test) and chromosomal (Micronucleus-cytome assay) mutations. Already, I2 and I3 complexes were considered mutagenic in the highest concentrations used. In light of the above, these results contribute to valuable data on the safe use of Cu(II) complexes. Considering the absence of mutagenicity and cytotoxicity of I1, this complex is a potential candidate for the development of a new drug to the treatment tuberculosis, while I2 and I3 require caution in its use. (AU)

• FAPESP's process: 17/16278-9 - Study of the genotoxicological potential and permeation assay with Caco-2 cells of metallic complexes with promising biological activities
• Grantee: Flávia Aparecida Resende Nogueira
• Support Opportunities: Regular Research Grants