Study of the mutagenic potential of copper (II) complexes with isoniazid by the micronucleus test

Abstract

Metallic complexes may be used in the treatment of various diseases due to their antibacterial, antiparasitic, anti-inflammatory and anti-tumor activities. In addition, they may act on chemo or radiotherapy and potentiate the action of a wide variety of drugs by modifying mechanisms of action. However, they can interact with DNA, causing damage that can be reflected in the increased of cancer and other undesirable health consequences such as infertility and genetic disorders. For this reason, is relevant to evaluate the mutagenic potential, at the chromosomal level, of Copper (II) complexes with Isoniazid (INH): [CuCl2 (INH) 2] _H2O (I1); [Cu (NCS) 2 (INH) 2] 5H 2 O (I 2) and [Cu (NCO) 2 (INH) 2]_4H2O (I3) in order to verify their safety to the genetic material and human health. These complexes were synthesized, characterized and provided by postdoctor Patrícia Silva Bento, from the Coordination and Organometallic Chemistry Group of the Chemistry Institute of Araraquara - UNESP, and selected for their promising activity against Escherichia coli, Staphylococcus aureus and Mycobacterium tuberculosis. In this study will be realized the micronucleus (MN) test with cytokinesis-block, using the human hepatocarcinoma cell line (HepG2), where the MN frequency in binucleate cells and the nuclear division index will be analyzed as parameters. The evaluation of mutagenic activity, at the gene level, has already been carried out using the reverse gene mutation test with Salmonella typhimurium, known as the Ames Test, through the pre-incubation test, using the TA98, TA97a, TA100 and TA102 S. thyphimurium strains, in the absence (-S9) and presence (+ S9) of metabolic activation. The results revealed absence of mutagenicity of the complexes I1 and I2, and evidence of mutagenicity in TA97a and TA100 lines, after metabolic activation. The performance of the micronucleus test will complement the results obtained in the Ames Test, contributing to confirm if the indication of mutagenicity at the gene level will perpetuate at chromosomal mutations. Thus, together, these assays will help understand the relationship of copper (II) complexes with possible induced DNA damage, providing reliable data to support future clinical trials because of promising antimicrobial activity already evidenced.