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

• Grant number: 16/17711-5
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2016
• End date: November 30, 2018
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Adelino Vieira de Godoy Netto
• Grantee: Adelino Vieira de Godoy Netto
• Host Institution: Instituto de Química (IQ). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated researchers: Claudia Bincoletto Trindade ; Fernando Rogério Pavan ; Fillipe Vieira Rocha ; José Clayston Melo Pereira ; Marlus Chorilli ; Patrícia Bento da Silva

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)

Scientific publications

(13)

(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)

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. (12/15486-3, 16/17711-5, 09/54011-8)

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.; et al. Orthopalladated acetophenone oxime compounds bearing thioamides as ligands: Synthesis, structure and cytotoxic evaluation. Inorganica Chimica Acta, v. 486, p. 617-624, FEB 24 2019. (12/15486-3, 16/17711-5)

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; et al. 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. (16/17711-5)

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. (12/15486-3, 16/17711-5, 14/11340-0)

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; et al. 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. (12/15486-3, 16/17711-5, 13/20156-5, 16/04201-9)

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.; et al. 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. (18/00187-7, 15/12098-0, 16/17711-5)

DE AMORIM, MARCELO R.; PAZ, TIAGO A.; PINTO, LUCIANO DA S.; HILARIO, FELIPE; ZANINI, CAMILA L.; AGUIAR, ANNA CAROLINE C.; SILVA, DEBORA E. S.; FURLAN, MAYSA; GUIDO, RAFAEL V. C.; BAUAB, TAIS M.; et al. New Isoquinoline Alkaloids from Paraphaeosphaeria sporulosa F03, a Fungal Endophyte Isolated from Paepalanthus planifolius. Planta Medica, v. N/A, p. 10-pg., 2022-01-19. (20/12904-5, 16/17711-5, 15/11058-5, 13/07600-3, 15/04899-3)

SOUZA, WESLEY A.; RAMOS, LUANA M. S.; ALMEIDA, ANGELINA M. DE; TEZUKA, DAIANE Y.; LOPES, CARLA D.; MOREIRA, MARIETE B.; ZANETTI, RENAN D.; NETTO, ADELINO V. G.; FERREIRA, FRANCIS B.; DE OLIVEIRA, RONALDO JUNIO; et al. Preparation, cytotoxic activity and DNA interaction studies of new platinum(II) complexes with 1,10-phenanthroline and 5-alkyl-1,3,4-oxa- diazol-2(3H)-thione derivatives. Journal of Inorganic Biochemistry, v. 237, p. 9-pg., 2022-09-13. (16/17711-5)

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; et al. 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. (15/12098-0, 16/25112-4, 14/02205-1, 09/54011-8, 19/11242-1, 16/17711-5)

VELASQUES, JECIKA M.; DE SOUZA, RONAN F. F.; SILVA, DEBORA E. S.; FARIAS, RENAN L.; ZANETTI, RENAN D.; MOREIRA, MARIETE B.; ELLENA, JAVIER; PEREIRA, JOSE C. M.; MAURO, ANTONIO E.; OLIVEIRA, ADRIANO B.; et al. Orthopalladated tetralone oxime compounds bearing tertiary phosphines: Synthesis, structure, biological and in silico studies. JOURNAL OF ORGANOMETALLIC CHEMISTRY, v. 958, JAN 15 2022. (12/15486-3, 16/17711-5)

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; et al. 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. (16/17711-5)

ZANETTI, RENAN D.; DA CUNHA, GISLAINE A.; MOREIRA, MARIETE B.; FARIAS, RENAN L.; DE SOUZA, RONAN F. F.; DE GODOY, PAULO R. D. V.; BRASSESCO, MARIA SOL; ROCHA, FILLIPE V.; LIMA, MAURO A.; MAURO, ANTONIO E.; et al. Orthopalladated N,N-dimethyl-1-phenethylamine compounds containing 2,6-lutidine: Synthesis, DNA binding studies and cytotoxicity evaluation. Polyhedron, v. 229, p. 11-pg., 2023-01-01. (09/54011-8, 12/15486-3, 16/17711-5)

DE MOURA, THALES REGGIANI; DE GODOY NETTO, ADELINO VIEIRA; MAURO, ANTONIO EDUARDO; MANENTE, FRANCINE ALESSANDRA; CARLOS, IRACILDA ZEPPONE; DA SILVA, ISABEL CRISTIANE; DA SILVA, PATRICIA BENTO; PAVAN, FERNANDO ROGERIO; ROCHA, FILLIPE VIEIRA; DEFLON, VICTOR MARCELO. Structure and cytotoxicity of palladium(II) complexes bearing N-ethyl-1-iminothiolate-3,5-dimethylpyrazole and triphenylphosphine. JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY, v. 22, p. 1-pg., 2017-07-01. (16/17711-5, 12/15486-3, 09/54011-8)