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Dinitrosyl complexes containing tiosemicarbazone, semicarbazone, tiadiazol or oxadiazole: synthesis, characterization and treatment against cancer

Grant number: 16/04329-5
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): June 01, 2016
Effective date (End): February 28, 2018
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
Principal Investigator:José Clayston Melo Pereira
Grantee:Renan Diego Zanetti
Host Institution: Instituto de Química (IQ). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil


Cancer is, currently, one of the leading causes of death in the world. Besides, it has been reported increasing cellular resistance of therapy using radiation with use of drugs. The enzyme glutathione S transferase system (GST) catalyze the conjugation of glutathione with cisplatin, restricting its anticancer action. In this project, we propose to use dinitrosyl iron complexes (DNIC) to reduce the problem of cellular resistance to antineoplastic agents. DNICs are formed inside cells upon cellular exposure to nitric oxide (NO) and bind to GST family of enzymes inhibiting its effect against anticancer drugs. Thus, it is proposed to develop DNICs of the type [Fe(NO)2X] (X = thiadiazole, thiosemicarbazone), wherein X would be a drug with antineoplastic activity. These binders are easily replaced by groups of the amino acid side chain of GSTs. Therefore, drug/binders would be replaced by GST enzymes of amino acids giving a possible synergism of enzyme inhibition and release of antineoplastic agents. 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) and normal cell (ATCC-PCS-201-012).

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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)
ZANETTI, RENAN DIEGO; GOTO, RENATA NISHIDA; LEOPOLDINO, ANDREIA MACHADO; MELO PEREIRA, JOSE CLAYSTON. Synthesis and characterization of iron nitrosyl complexes for anticancer activity. JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY, v. 22, p. 1-pg., . (16/04329-5)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
ZANETTI, Renan Diego. Dinitrosyl iron complexes containing thiadiazole or thiosemicarbazone derived from cinnamaldehyde: synthesis, characterization and potential antitumor application. 2018. Master's Dissertation - Universidade Estadual Paulista (Unesp). Instituto de Química. Araraquara Araraquara.

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