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Synthesis, characterization and evaluation of DNA intercalation capacity of Pt(II) complexes bearing 1,10-phenanthroline and derivatives

Grant number: 19/17584-1
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): November 01, 2019
Effective date (End): December 31, 2020
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
Principal researcher:Fillipe Vieira Rocha
Grantee:Debora Pinheiro Felix
Home Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil


Cancer arises from a genetic mutation that occurs inside of the nucleus of the cell, different types of cancer are the second cause of the death in the world. In fact, one each six deaths are related to the disease. Although only 3 complexes are approved for clinical use, currently, Pt (II) compounds participate in approximately 50% of cancer treatments. However, these compounds have several side effects, highlighting: nephrotoxicity and neurotoxicity. Additionally, some kinds of tumours are resistant to the treatments with Pt(II) compounds. A conformational change in the coordination sphere of the complexes could modify their mechanism of action, attenuating these undesirable effects. The introduction of planar aromatic ligands into the complexes structure would allow an intercalative interaction between the platinum compounds and DNA. Thus, the ligands 1,10-phenanthroline (phen), 1,10-phenanthroline-5,6-dione (qphen) and pyrazino [2,3-f] [1,10] phenanthroline-2,3-dicarbonitrile ( DMT) and its platinum (II) complexes appear as an alternative in obtaining cytotoxic agents. Therefore, present project aims to synthesize three new platinum (II) complexes containing two phenantroline-derived of general formula: [Pt(DMT)2](PF6)2; [Pt(DMT)(qphen)](PF6)2; [Pt(DMT)(phen)](PF6)2. All the compounds will be characterized by NMR, IR, UV-Vis and elemental analysis. The possible interaction between compounds and DNA will be evaluated through DNA viscosity assay, ethidium bromide competition, UV/Vis DNA titration and DNA electrophoretic mobility assay. The cytotoxicity of the most promising complexes will be investigated against tumor and non-tumor cell lines.

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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)
ALMEIDA, VITOR Y. G.; ROCHA, JOSIAS S.; FELIX, DEBORA P.; OLIVEIRA, GABRIELA P.; LIMA, MAURO A.; FARIAS, RENAN L.; ZANETTI, RENAN D.; NETTO, ADELINO V. G.; ZAMBOM, CAROLINA R.; GARRIDO, SAULO S.; ROCHA, V, FILLIPE. Cytotoxicity and Antibacterial Activity of Silver Complexes Bearing Semicarbazones and Triphenylphosphine. CHEMISTRYSELECT, v. 5, n. 46, p. 14559-14563, DEC 11 2020. Web of Science Citations: 0.

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