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Investigations on the biological activity of Heterodinuclear complexes based on copper and platinum

Grant number: 12/17671-2
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): February 01, 2013
Effective date (End): September 30, 2014
Field of knowledge:Physical Sciences and Mathematics - Chemistry
Principal Investigator:Ana Maria da Costa Ferreira
Grantee:Esther Escribano Aranda
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:11/50318-1 - Development of compounds with pharmacological or medicinal interest and of systems for their transport, detection and recognition in biological media, AP.TEM

Abstract

In the literature, some dinuclear complexes have been already prepared in order to improve the anticancer activity of potential metallodrugs. Examples include platinum, copper, and ruthenium complexes. Herein, investigations on the biological activity of heterodinuclear complexes containing copper and platinum are proposed, in order to ally the ability of binding to DNA and redox activity of copper ion to the already known nuclease properties of platinum. Based on previous studies, oxindolimines will be used as ligands for the copper, while amines, and chloride ligands for the platinum. All the isolated species will be characterized by diverse techniques (UV/Vis, IR, EPR, 1H-RMN and 195Pt-RMN spectroscopies, thermogravimetric and elemental analyses). An improvement in the anticancer activity of the resulting species, regarding mononuclear species of each metal, is expected, since the novel species can probably generate reactive oxygen species in addition to efficiently bind to the DNA and cause consequent oxidative damage. The proposed studies include further investigations of possible interactions of the prepared metal species with selected biomolecules (specific proteins and nucleic acids), and consequent intracellular oxidative damage, as degradation of proteins, DNA cleavage and induced apoptosis by using different methodology (CD, SDS Page electrophoresis, confocal microscopy, ESI-MS/MS, fluorescence, etc).