Resumo
Linha de Pesquisa: Química Inorgânica Sintética e Estrutural: Bioinorgânica e Metalofármacos
O nosso grupo desenvolve pesquisas na área de Química Bioinorgânica Medicinal, com ênfase no estudo de metalofármacos e de sistemas de liberação sustentada. Os trabalhos envolvem a concepção, a síntese e a investigação de propriedades de compostos metálicos, particularmente de rutênio e de cobre, que possam apresentar atividade farmacológica/medicinal (anticancer, anti-inflamatória, antimicrobiana, etc.). Novos compostos são preparados, caracterizados estruturalmente, e são investigados com relação à suas reatividades química e bioquímica, e à suas atividades biológica e farmacológica. O grupo é pioneiro na síntese de compostos de dirutênio com fármacos anti-inflamatórios não-esteróides, que tem demonstrado boa atividade para glioblastoma multiforme (GBM) - cancer cerebral de difícil prognóstico. Materiais híbridos combinados, contendo micro/nano-partículas dos fármacos encapsulados e/ou imobilizados em biopolímeros e/ou em matrizes inorgânicas, particularmente MOFs (metal organic-frameworks), são preparados visando à obtenção sistemas de liberação sustentada. Dispomos de infra-estrutura para efetuar sínteses inorgânicas convencionais, hidrotérmicas e via microondas, de instrumentos para realizar secagem por spray-drying e fazer estudos de dissolução de fármacos, e de equipamentos para emprego das técnicas de espectroscopia eletrônica UV-VIS-IR, espectroscopia vibracional FTIR, difratometria de raios X (DRX), análise térmica (TG/DSC/MS), cromatografia líquida de alta eficiência (HPLC), medidas de susceptibilidade magnética e outras. Também utilizamos técnicas que estão disponíveis na Central Analítica do IQ-USP, tais como, análises elementares (C,H,N,Cl and ICP-AES), espectrometria de massas (CG-MS, LC-MS), microscopia eletrônica de varredura (MEV), dicroísmo circular (DC), dentre outras.
Summary
Our research team develops research in the field of Medicinal Bioinorganic Chemistry with focus on the study of metallopharmaceuticals and sustained drug delivery systems. Our research projects mainly involve the design, the synthesis and the investigation of properties of metal compounds, in particular ruthenium and copper compounds, that may show pharmacological/medicinal properties (anticancer, anti-inflammatory, antimicrobial, etc.). The group is pionner of studying diruthenium compounds containing non-steroidal anti-inflammatory drugs which were found to show good activity against glioblastoma multiforme (GBM) - a brain cancer having poor prognosis. Novel compounds are prepared, structurally characterized, and have their chemical and biochemical reactivity as well as biological and pharmacological properties investigated. Combined hybrid materials containing micro/nano-particles of drugs encapsulated and/or immobilized into biopolymers and/or inorganic matrices, in particular, MOFs (metal-organic frameworks), are prepared as systems for drug delivery. The laboratory offers conditions for conventional, hydrothermal and microwave assisted inorganic synthesis, spray-drying and drug dissolution studies, and also provides equipments for analysis by UV-VIS-IR electronic spectroscopy, FTIR vibrational spectroscopy, powder X-ray diffractometry (XRD), thermal analysis (TG/DSC/MS), high performance liquid chromatography (HPLC), magnetic susceptibility measurements, among others. We also work with some techniques that are available at the IQ Analytical Centre, such as elemental analysis (C,H,N,Cl and ICP-AES), mass spectrometry (CG-MS, LC-MS), scanning electron microscopy (SEM), circular dichroism (CD).
Produção científica
Curriculo (Sistema Lattes - CNPq)
Curriculo (Sistema Researcher ID)
Hanif-Ur-Rehman, Bárbara Fornaciari, Samara R. Alves, Alison Colquhoun, Denise de Oliveira Silva. 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, 40 (7), 549-565, 2023.
Samara R. Alves, Rodrigo L.S.R. Santos, Bárbara Fornaciari, Alison Colquhoun, Denise de Oliveira Silva. A novel μ-oxo-diruthenium(III,III)-ibuprofen-(4-aminopyridine) chloride derived from the diruthenium(II,III)-ibuprofen paddlewheel metallodrug shows anticancer properties. Journal of Inorganic Biochemistry 225, 111596, 2021.
Hanif-Ur-Rehman, 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, 31 (11), 2331–2341, 2020.
Samara R. Alves, Alison Colquhoun, Xiao Yu Wu, Denise de Oliveira Silva. Synthesis of terpolymer-lipid encapsulated diruthenium(II,III)-antiinflammatory metallodrug nanoparticles to enhance activity against glioblastoma cancer cells. Journal of Inorganic Biochemistry 205 ,110984, 2020.
Julie P. G. Tabares, Rodrigo L.S.R. Santos, Jefferson L. Cassiano, Marcio H. Zaim, Joao Honorato, Alzir A. Batista, Sarah F. Teixeira, Adilson K. Ferreira, Rommel B. Viana, Sandra Q. Martinez, Antonio C. Stabile, Denise de Oliveira Silva. 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 489, 27–38, 2019.
Samara R. Alves Rico, Azhar Z. Abbasi, Geise Ribeiro, Taksim Ahmed, Xiao Yu Wu, Denise de Oliveira Silva. 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, 9, 10701–10714, 2017.
Hanif-Ur-Rehman, Tatiana E. Freitas, Renata N. Gomes, Alison Colquhoun, Denise de Oliveira Silva. Axially-modified paddlewheel diruthenium(II,III)-ibuprofenato metallodrugs and the influence of the structural modification on U87MG and A172 human glioma cell proliferation, apoptosis, mitosis and migration. Journal of Inorganic Biochemistry 165, 181–191, 2016.
Luigi Messori, Tiziano Marzo, Rute N. F. Sanches, Hanif-Ur-Rehman, Denise de Oliveira Silva, Antonello Merlino. Unusual Structural Features in the Lysozyme Derivative of the Tetrakis(acetato)chloridodiruthenium(II,III) Complex. Angewandte Chemie International Edition, 53, 6172 –6175, 2014.
Denise de Oliveira Silva. Ruthenium compounds targeting cancer therapy. In: Atta-ur-Rahman and M.I. Choudhary, eds. Frontiers in anti-cancer drug discovery. Vol. 4. United Arab Emirates: Bentham Science Publishers, 88–156, 2014.
Rodrigo L. S. R. Santos, Rudi van Eldik, Denise de Oliveira Silva. Kinetic and mechanistic studies on reactions of diruthenium(II,III) with biologically relevant reducing agents. Dalton Transactions, 42, 16796–16805, 2013.
Denise de Oliveira Silva, Perspectives for novel mixed diruthenium-organic drugs as metallopharmaceuticals in cancer therapy. Anti-cancer agents in medicinal chemistry, 10 (4), 312–323, 2010.
