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Study of ruthenium metallodrugs and nanoparticle systems of these metallodrugs TARGENTING cancer therapy

Grant number: 18/02297-4
Support type:Regular Research Grants
Duration: May 01, 2018 - April 30, 2020
Field of knowledge:Physical Sciences and Mathematics - Chemistry
Principal Investigator:Denise de Oliveira Silva
Grantee:Denise de Oliveira Silva
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The research in our laboratory is focused on the study of metallodrugs to open new perspectives in the fields of bioinorganic and pharmacology with the development of new drug candidates and new formulations that may show potential impact on human health treatment. The work is mainly directed to synthesis, characterization, reactivity and biological activity of ruthenium compounds bearing bioactive ligands such as the non-steroidal anti-inflammatory drugs (NSAIDs). We have reported that metal-metal multiply bonded dinuclear complexes having NSAIDs coordinated to Ru2(II,III) cores exhibit in vitro and in vivo anticancer activity in glioma models such as the highly malignant brain tumor glioblastoma. We have also demonstrated that solid polymer-lipid nanoparticle systems of Ru2-NSAIDs complexes are active against breast and prostate cancer cell lines. The main objectives of the present project are: a) to broad the research on synthesis of new Ru2(II,III) dinuclear and Ru(II) mononuclear complexes having NSAIDs or amide-modified NSAIDs to elucidate the influence of the drug and the Ru complex structures on both the chemical reactivity and the biological activity; b) to expand studies on interactions of metallodrugs with target-biomolecules, in particular, albumin, DNA and small molecules as N-bases, amino acids and imidazole-mimetics; c) to investigate biocompatible nanoparticle systems aiming the development of new formulations with potential to increase efficacy of the metallodrugs targeting cancer therapy. (AU)