Evaluation of the mutagenic activity of metal complexes with promising biological activities

• Grant number: 14/22121-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): April 01, 2015
• Effective date (End): March 31, 2016
• Field of knowledge: Biological Sciences - Genetics - Mutagenesis
• Principal Investigator: Flávia Aparecida Resende Nogueira
• Grantee: Mariana Cristina Solcia
• Host Institution: Pró-Reitoria Acadêmica. Universidade de Araraquara (UNIARA). Associação São Bento de Ensino. Araraquara , SP, Brazil

Abstract

The use of metal complexes with bioactive ligands has been targeted for the development of new drugs with biological activities. Thus, it becomes extremely important to know the mechanisms of action of these complexes, so you can set your real clinical potential. The research group in Medicinal Chemistry and Regenerative Medicine (QUIMMERA) of the University Center of Araraquara (Uniara), have been developing studies on the synthesis and characterization of metal complexes with potential antibacterial and antitumor activity, in partnership with other institutions. Thus, this work aims at the integration of the Mutagenesis area of the work carried out by the group, in order to assess the potential of DNA damage, since it is already well understood the relationship between mutagenicity and carcinogenicity. So, the aim of this study will be to evaluate the mutagenic activity of metallodrugs: gold (I) with furosemide (Au(I)-fur), platinum with gabapentin (Pt-GAB) and silver with hydrochlorothiazide (HCZ-Ag), by means of reverse mutation assay with Salmonella typhimurium, also known as the Ames test. These complexes were previously selected by show promising antibacterial activity. The Ames test uses bacteria as sensitive indicators of DNA damage, and a rat liver homogenate (S9 microsomal fraction) for metabolic conversion of carcinogens to their active mutagenic forms. In the present study, the Ames testwas performed using TA98, TA100, TA97 and TA102 strains of S. typhimuriumin the absence (-S9) and presence (+S9) of metabolic activation system. The obtained results will serve to evaluate the mutagenic capacity of these metal complexes, through its interaction with DNA, and thus provide reliable data to give subsidies to future clinical research.