Investigations on the Biological Activity of Heterodinuclear Complexes based on Copper and Platinum

• Grant number: 12/17671-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: February 01, 2013
• End date: September 30, 2014
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Ana Maria da Costa Ferreira
• Grantee: Esther Escribano Aranda
• Host 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).

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ARANDA, ESTHER ESCRIBANO; DA LUZ, JULIANA SILVA; OLIVEIRA, CARLA COLUMBANO; DIVINA PETERSEN, PHILIPPE A.; PETRILLI, HELENA M.; DA COSTA FERREIRA, ANA M.. Heterobinuclear copper(II)-platinum(II) complexes with oxindolimine ligands: Interactions with DNA, and inhibition of kinase and alkaline phosphatase proteins. Journal of Inorganic Biochemistry, v. 203, FEB 2020. (11/50318-1, 13/07937-8, 12/17671-2)