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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