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INVESTIGATION OF THE ANTITUMOR POTENTIAL OF PALLADIUM(II) COMPOUNDS CONTAINING ORTHOMETALLATED OR N,S-DONOR LIGANDS

Abstract

This project deals with the synthesis, characterization and evaluation of the antitumor potential of compounds [PdCl(C2,N-ox)(PR3)], [Pd2Cl2(C2,N-ox)2(µ-PP)] and [PdCl(CINTSC)(PR3)] (PR3 = tertiary monodentate phosphanes, PP = diphosphanes; ox = orthometallated oximes functionalized or not, CINTSC = thiosemicabazones derived from cinmaldehyde). The compounds will be characterized by elemental analysis, IR and NMR spectroscopies, ESI/MS mass spectrometry, thermogravimetry (TG) and single crystal X-ray diffraction methods. The cytotoxicity of the compounds towards normal and tumor cells together with their ability to inhibit toposiomerase IIa and catepsin B will be evaluated. The compounds with promising results will be further selected to studies about the involvement of the lysosomal mitochondrial axis in their respective mechanism of action. The induction potential of apoptosis/necrosis and cleavage of caspase-3 mediated by these selected compounds will be also evaluated. Aiming at improving solubility and selectivety, these Pd(II) compounds will be incorporated into nanostructured lipid systems, which will be characterized by dynamic light scattering, polarized light microscopy, zeta potential, rheological behavior and thermal analysis. In sillico studies will be carried out in order to gain more knowledge about the possible mechanism involved in inhibitory enzymatic activity induced by these complexes. (AU)

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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)
FARIAS, R. L.; POLEZ, A. M. R.; SILVA, D. E. S.; ZANETTI, R. D.; MOREIRA, M. B.; BATISTA, V. S.; REIS, B. L.; NASCIMENTO-JUNIOR, N. M.; ROCHA, V, F.; LIMA, M. A.; OLIVEIRA, A. B.; ELLENA, J.; SCARIM, C. B.; ZAMBOM, C. R.; BRITO, L. D.; GARRIDO, S. S.; MELO, A. P. L.; BRESOLIN, L.; TIRLONI, B.; PEREIRA, J. C. M.; NETTO, A. V. G. In vitro and in silico assessment of antitumor properties and biomolecular binding studies for two new complexes based on Ni-II bearing k(2)N, S-donor ligands. Materials Science & Engineering C-Materials for Biological Applications, v. 121, FEB 2021. Web of Science Citations: 0.
DE MOURA, THALES REGGIANI; ZANETTI, RENAN DIEGO; SILVA, DEBORA EDUARDA SOARES; DE FARIAS, RENAN LIRA; MAURO, ANTONIO EDUARDO; PEREIRA, JOSE CLAYSTON MELO; DE SOUZA, ALINE APARECIDA; DA SILVA SIQUEIRA, FABIO; DE SOUZA JUDICE, WAGNER ALVES; LIMA, MAURO ALMEIDA; ROCHA, FILLIPE VIEIRA; DEFLON, VICTOR MARCELO; VIEIRA DE GODOY NETTO, ADELINO. Palladium(ii) complexes bearing 1-iminothiolate-3,5-dimethylpyrazoles: synthesis, cytotoxicity, DNA binding and enzymatic inhibition studies. NEW JOURNAL OF CHEMISTRY, v. 44, n. 45, p. 19891-19901, DEC 7 2020. Web of Science Citations: 0.
FURQUIM DE CAMARGO, BRUNA ALMEIDA; SOARES SILVA, DEBORA EDUARDA; DA SILVA, ANDERSON NORONHA; CAMPOS, DEBORA LEITE; MACHADO RIBEIRO, TAMARA RENATA; MIELI, MARIA JULIA; TEIXEIRA ZANATTA, MELINA BORGES; DA SILVA, PATRICIA BENTO; PAVAN, FERNANDO ROGERIO; MOREIRA, CRISTIANO GALLINA; RESENDE, FLAVIA APARECIDA; MENEGARIO, AMAURI ANTONIO; CHORILLI, MARLUS; DE GODOY NETTO, ADELINO VIEIRA; BAUAB, TAIS MARIA. New Silver(I) Coordination Compound Loaded into Polymeric Nanoparticles as a Strategy to Improve In Vitro Anti-Helicobacter pylori Activity. MOLECULAR PHARMACEUTICS, v. 17, n. 7, p. 2287-2298, JUL 6 2020. Web of Science Citations: 0.
ROCHA, FILLIPE V.; FARIAS, RENAN L.; LIMA, MAURO A.; BATISTA, VICTOR S.; NASCIMENTO-JUNIOR, NAILTON M.; GARRIDO, SAULO S.; LEOPOLDINO, ANDREA M.; GOTO, RENATA N.; OLIVEIRA, ADRIANO B.; BECK, JOHANNES; LANDVOGT, CHRISTIAN; MAURO, ANTONIO E.; NETTO, ADELINO V. G. Computational studies, design and synthesis of Pd(II)-based complexes: Allosteric inhibitors of the Human Topoisomerase-II alpha. Journal of Inorganic Biochemistry, v. 199, OCT 2019. Web of Science Citations: 7.
ESPURI, PATRICIA FERREIRA; DOS REIS, LARISSA LUIZA; PELOSO, EDUARDO DE FIGUEIREDO; GONTIJO, VANESSA SILVA; COLOMBO, FABIO ANTONIO; NUNES, JULIANA BARBOSA; DE OLIVEIRA, CARINE ERVOLINO; DE ALMEIDA, EDUARDO T.; SILVA, DEBORA E. S.; BORTOLETTO, JESSICA; SEGURA, DANIEL FONSECA; NETTO, ADELINO V. G.; MARQUES, MARCOS JOSE. Synthesis and evaluation of the antileishmanial activity of silver compounds containing imidazolidine-2-thione. JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY, v. 24, n. 3, p. 419-432, MAY 2019. Web of Science Citations: 2.
DE SOUZA, RONAN F. F.; DA CUNHA, GISLAINE A.; PEREIRA, JOSE C. M.; GARCIA, DANIEL M.; BINCOLETTO, CLAUDIA; GOTO, RENATA N.; LEOPOLDINO, ANDREIA M.; DA SILVA, ISABEL C.; PAVAN, FERNANDO R.; DEFLON, VICTOR M.; DE ALMEIDA, EDUARDO T.; MAURO, ANTONIO E.; NETTO, ADELINO V. G. Orthopalladated acetophenone oxime compounds bearing thioamides as ligands: Synthesis, structure and cytotoxic evaluation. Inorganica Chimica Acta, v. 486, p. 617-624, FEB 24 2019. Web of Science Citations: 2.
BOZZA, GABRIELA F.; DE FARIAS, RENAN L.; DE SOUZA, RONAN F. F.; ROCHA, V, FILLIPE; BARRA, V, CAROLINA; DEFLON, VICTOR M.; DE ALMEIDA, EDUARDO T.; MAURO, ANTONIO E.; NETTO, ADELINO V. G. Palladium orthometallated complexes containing acetophenoneoxime: Synthesis, crystal structures and hirshfeld surface analysis. Journal of Molecular Structure, v. 1175, p. 195-207, JAN 5 2019. Web of Science Citations: 3.
DE MOURA, THALES R.; CAVALCANTI, SAHRA L.; DE GODOY, PAULO R. D. V.; SAKAMOTO-HOJO, ELZA T.; ROCHA, FILLIPE V.; DE ALMEIDA, EDUARDO T.; DEFLON, VICTOR M.; MAURO, ANTONIO E.; NETTO, ADELINO V. G. Synthesis, characterization and antitumor activity of palladium(II) complexes of imidazolidine-2-thione. TRANSITION METAL CHEMISTRY, v. 42, n. 6, p. 565-574, SEP 2017. Web of Science Citations: 6.

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