Anticancer metallodrugs of ruthenium containing bioactive ligands: synthesis, interaction with biomolecules and preparation of biocompatible nanoparticle drug delivery systems

• Grant number: 14/23047-5
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2015
• End date: June 30, 2017
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Denise de Oliveira Silva
• Grantee: Denise de Oliveira Silva
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Ruthenium compounds containing bioactive ligands such as non-steroidal anti-inflammatory drugs (NSAIDs) are the main focus of research in our laboratory with the purpose of finding novel metallodrugs. Compounds containing multiple metal-metal bonded Ru2(II,III) cores coordinated to NSAIDs have been found in pre-clinical studies to show anticancer properties against models of the highly malignant cerebral tumor glioblastoma multiforme (GBM). The objective of the present project is to expand our researches on this topic according to three main directions: a) synthesis and characterization of new Ru2(II,III)-NSAID complexes (with focus on structural modifications) and novel Ru(II) organometallic compounds with NSAIDs in their structures; b) studies on the interactions of the complexes with target biomolecules, e.g., amino acids and their mimetics, N-heterocyclic bases, blood proteins (human serum albumin and transferrin), DNA and oligonucleotides; c) preparation and investigation of the properties of new biocompatible nanoparticle hybrid systems formed by the interactions of the Ru2(II,III)-ibuprofen complex, the lead metallodrug, and its derivatives, with chitosans and lipids. These studies will make possible to extend the Ru-NSAID series of metallodrugs in order to try to find correlations between molecular structure and chemical and biological properties, to elucidate possible biomolecule targets and modes of action, and to exploit the viability of developing biocompatible hybrid systems for transport and drug delivery. The research may open new perspectives for bioinorganic, pharmacology and biomedical sciences by means of the development of novel drug candidates and new formulations with potential impact on the field of health targeting glioma brain cancer therapy. (AU)

Scientific publications

(8)

(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)

MARCIO HAYASHI; SAMARA R. ALVES; IGUATINÃ M. COSTA; DENISE DE OLIVEIRA SILVA. Self-Assembled Nanoparticles of Diruthenium(II,III)-Ibuprofen Anticancer Metallodrug. Journal of the Brazilian Chemical Society, v. 31, n. 11, p. 2331-2341, 2020-10-30. (14/23481-7, 16/23028-6, 14/23047-5)

GAITAN TABARES, JULIE PAULINE; SANTOS, RODRIGO LUIS S. R.; CASSIANO, JEFFERSON LUIZ; ZAIM, MARCIO H.; HONORATO, JOAO; BATISTA, ALZIR A.; TEIXEIRA, SARAH F.; FERREIRA, ADILSON KLEBER; VIANA, ROMMEL B.; MARTINEZ, SANDRA QUISPE; et al. A Ru(II)-p-cymene compound bearing naproxen-pyridineamide. Synthesis, spectroscopic studies, computational analysis and in vitro anticancer activity against lung cells compared to Ru(II)-p-cymene-naproxen and the corresponding drug ligands. Inorganica Chimica Acta, v. 489, p. 27-38, APR 1 2019. (14/23047-5, 15/18528-7)

REHMAN, HANIF-UR-; FORNACIARI, BARBARA; ALVES, SAMARA R.; COLQUHOUN, ALISON; SILVA, DENISE DE OLIVEIRA. Diruthenium(II-III)-ibuprofen-loaded chitosan-based microparticles and nanoparticles systems: encapsulation, characterisation, anticancer activity of the nanoformulations against U87MG human glioma cells. Journal of Microencapsulation, v. 40, n. 7, p. 17-pg., 2023-09-25. (14/23047-5, 14/23481-7)

SILVA RIBEIRO SANTOS, RODRIGO LUIS; FERNANDES SANCHES, RUTE NAZARE; SILVA, DENISE DE OLIVEIRA. Spectroscopic studies on interactions of the tetrakis(acetato) chloridodiruthenium(II,III) complex and the Ru-2(II,III)-NSAID-derived metallodrugs of ibuprofen and ketoprofen with human serum albumin. Journal of Coordination Chemistry, v. 68, n. 17-18, SI, p. 3209-3228, 2015. (14/23047-5, 11/06592-1)

ALVES RICO, SAMARA R.; ABBASI, AZHAR Z.; RIBEIRO, GEISE; AHMED, TAKSIM; WU, XIAO YU; SILVA, DENISE DE OLIVEIRA. Diruthenium(II,III) metallodrugs of ibuprofen and naproxen encapsulated in intravenously injectable polymer-lipid nanoparticles exhibit enhanced activity against breast and prostate cancer cells. NANOSCALE, v. 9, n. 30, p. 10701-10714, AUG 14 2017. (14/23047-5, 14/23481-7, 15/24252-4, 11/06592-1)

SILVA RIBEIRO SANTOS, RODRIGO LUIS; FERNANDES SANCHES, RUTE NAZARE; SILVA, DENISE DE OLIVEIRA. Spectroscopic studies on interactions of the tetrakis(acetato) chloridodiruthenium(II,III) complex and the Ru-2(II,III)-NSAID-derived metallodrugs of ibuprofen and ketoprofen with human serum albumin. Journal of Coordination Chemistry, v. 68, n. 17-18, p. 20-pg., 2015-01-01. (11/06592-1, 14/23047-5)

ALVES, SAMARA RODRIGUES; COLQUHOUN, ALISON; WU, XIAO YU; SILVA, DENISE DE OLIVEIRA. Synthesis of terpolymer-lipid encapsulated diruthenium(II,III)-anti-inflammatory metallodrug nanoparticles to enhance activity against glioblastoma cancer cells. Journal of Inorganic Biochemistry, v. 205, APR 2020. (14/23481-7, 15/24252-4, 14/23047-5)

ALVES, SAMARA R.; SANTOS, RODRIGO L. S. R.; FORNACIARI, BARBARA; COLQUHOUN, ALISON; SILVA, DENISE DE OLIVEIRA. A novel mu-oxo-diruthenium(III,III)-ibuprofen-(4-aminopyridine) chloride derived from the diruthenium(II,III)-ibuprofen paddlewheel metallodrug shows anticancer properties. Journal of Inorganic Biochemistry, v. 225, DEC 2021. (14/23481-7, 14/23047-5)