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Anti-inflammatory and antitumor metallotherapeutic drugs: reactivity, properties and interactions with biocompatible hosts

Grant number: 11/06592-1
Support Opportunities:Regular Research Grants
Duration: April 01, 2012 - March 31, 2014
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


This project has the purpose of studying metallotherapeutic drugs as strategic field of bioinorganic with multidisciplinary character involving pharmacological and biological aspects. Previous works of our group gave evidences for anti-inflammatory activity of copper and ruthenium metallodrugs with NSAIDs (non-steroidal anti-inflammatory drugs) and for antiproliferative action of diruthenium metallodrugs against C6 cells (rat glioma) - model for glioblastoma multiform (GBM), a type of malignant brain tumor. Promising pharmacological properties of metallo-NSAIDs, mainly diruthenium-NSAIDs (for which our group is pioneer in studies), open good perspectives for broader and detailed studies. Based on these perspectives, the main goal of the present proposal is to continue our studies with the aim of: preparing novel metallo-NSAIDs; improving characterization studies; investigating chemical and physical-chemistry behavior; studying the reactivity of metallo-NSAIDs towards biomolecules; investigating interactions of the metallo-NSAIDs with biocompatible hosts (cyclodextrins, cellulose derivatives and chitosans) to prepare biocompatible organic-bioinorganic hybrid materials. The major purpose is to get a more complete data file that might help us to establish correlations among molecular structure, reactivity and properties aiming to the elucidation of pharmacological and biological activity of these compounds. Additionally, the project includes the study of viability to prepare hybrid materials that can act as carrier and/or drug (sustained or controlled) delivery systems of metallodrugs aiming to potential future applications in the field of health/biomedicine. (AU)

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Scientific publications (6)
(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)
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, . (14/23047-5, 14/23481-7, 15/24252-4, 11/06592-1)
MARTINS, DOUGLAS DE J.; HANIF-UR-REHMAN; ALVES RICO, SAMARA R.; COSTA, IGUATINA DE M.; PIO SANTOS, ANDREA C.; SZSZUDLOWSKI, RACHEL G.; SILVA, DENISE DE OLIVEIRA. Interaction of chitosan beads with a copper-naproxen metallodrug. RSC ADVANCES, v. 5, n. 109, p. 90184-90192, . (05/60596-8, 11/06592-1)
SILVA RIBEIRO SANTOS, RODRIGO LUIS; VAN ELDIK, RUDI; SILVA, DENISE DE OLIVEIRA. Kinetic and mechanistic studies on reactions of diruthenium(II,III) with biologically relevant reducing agents. DALTON TRANSACTIONS, v. 42, n. 48, p. 16796-16805, . (05/60596-8, 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, SI, p. 3209-3228, . (14/23047-5, 11/06592-1)
MIYAKE, JULIANO ANDREOLI; BENADIBA, MARCEL; RIBEIRO, GEISE; SILVA, DENISE DE OLIVEIRA; COLQUHOUN, ALISON. Novel Ruthenium - Gamma-linolenic Acid Complex Inhibits C6 Rat Glioma Cell Proliferation In Vitro and in the Orthotopic C6 Model In Vivo After Osmotic Pump Infusion. ANTICANCER RESEARCH, v. 34, n. 4, SI, p. 1901-1911, . (11/06592-1, 05/60596-8)
MESSORI, LUIGI; MARZO, TIZIANO; FERNANDES SANCHES, RUTE NAZARE; HANIF-UR-REHMAN; SILVA, DENISE DE OLIVEIRA; MERLINO, ANTONELLO. Unusual Structural Features in the Lysozyme Derivative of the Tetrakis(acetato)chloridodiruthenium(II,III) Complex. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, v. 53, n. 24, p. 6172-6175, . (11/06592-1)

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