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Dinitrosyl complexes containing thiol and/or thiosemicarbazone : synthesis, characterization and treatment against cancer

Grant number: 15/12098-0
Support type:Regular Research Grants
Duration: October 01, 2015 - September 30, 2017
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
Principal researcher:José Clayston Melo Pereira
Grantee:José Clayston Melo Pereira
Home Institution: Instituto de Química (IQ). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Assoc. researchers:Adelino Vieira de Godoy Netto ; Adriano Bof de Oliveira

Abstract

Cancer is disease, which caused 12% of all human deaths worldwide each year. The combination of the two well known drugs, Cisplatin and fluorouracil, has been used for treatment of cancer. However, recently, it have been reported that the enzyme system glutathione/glutathione s-transferases (GSH/GSTs) causes tumor cells increasingly resistant to the treatment. This project proposes to use DNICs as alternative drug to cisplatin. DNICs are formed inside cells upon cellular exposure to nitric oxide (NO) and are known to bind strongly to and inhibit the GST enzyme family. Thus, we propose to synthesize and characterize new DNICs of the type [Fe(NO)2(X)2] (X = 6-mercaptopurine, captopril, thiosemicarbazones and thiocarbamoylpirazol), and [Fe(NO)2XY] (X = 6-mercaptopurine, Y = captopril, thiosemicarbazones and thiocarbamoylpirazol), where X and Y are anticancer drugs with distinct mechanisms of action. The DNIC ligands other than NO are readily replaced by GSTs aminoacid side chain groups, leading to a possible synergism of inhibiting GST and releasing anticancer agents in the same cell and simultaneously. The citotoxicity effects of these new DNIC compounds will be tested in assays using the human tumor cell lines MCF7 (ATCC - HTB-22), CHL-1(ATCC-CRL-9446), PC-03 (ATCC CRL 1435), HT-29 (ATCC HTB-38) e SNU-1 (ATCC CRL - 5971) e normal cell (ATCC - PCS-201-012) (AU)

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Scientific publications (5)
(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.
DE OLIVEIRA, GABRIELA PORTO; BRESOLIN, LEANDRO; FLORES, DARLENE CORREIA; DE FARIAS, RENAN LIRA; DE OLIVEIRA, ADRIANO BOF. Crystal structure of (2E)-3-[4-(dimethylamino)phenyl]-1-(thiophen-2-yl)prop-2-en-1-one. ACTA CRYSTALLOGRAPHICA SECTION E-CRYSTALLOGRAPHIC COMMUNICATIONS, v. 73, n. 4, p. 476+, APR 2017. Web of Science Citations: 0.
DE OLIVEIRA, ADRIANO BOF; BECK, JOHANNES; LANDVOGT, CHRISTIAN; DE FARIAS, RENAN LIRA; SANTOS FEITOZA, BARBARA REGINA. Crystal structure of N-ethyl-2-(1,2,3,4-tetrahydronaphthalen-1-ylidene)hydrazinecarbothioamid e. ACTA CRYSTALLOGRAPHICA SECTION E-CRYSTALLOGRAPHIC COMMUNICATIONS, v. 73, n. 2, p. 291+, FEB 2017. Web of Science Citations: 1.
VELASQUES, JECIKA MACIEL; GERVINI, VANESSA CARRATU; BORTOLUZZI, ADAILTON JOAO; DE FARIAS, RENAN LIRA; DE OLIVEIRA, ADRIANO BOF. Crystal structure of (3E)-5-nitro-3-(2-phenylhydrazinylidene)-1H-indol-2(3H)-one. ACTA CRYSTALLOGRAPHICA SECTION E-CRYSTALLOGRAPHIC COMMUNICATIONS, v. 73, n. 2, p. 168+, FEB 2017. Web of Science Citations: 0.

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