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synthesis, characterization and anticancer activity of iron and ruthenium complexes with thiadiazole ligand

Grant number: 19/17762-7
Support type:Regular Research Grants
Duration: October 01, 2021 - September 30, 2023
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 ; Saulo Santesso Garrido

Abstract

Cancer is a disease, which caused around 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 that disease. However, it has been reported that the enzyme system glutathione/glutathione s-transferases (GSH/GSTs) causes tumor cells resistant to the treatment of cancer. Herein, we propose to use dinitrosyl iron complexes (DNIC) as alternative drug to cisplatin and fluorouracil. DNICs are formed inside cells upon cellular exposure to nitric oxide (NO). Beside, DNICs can bind strongly to and inhibit the GST enzyme family. Thus, we propose to synthesize and characterize new complexes of the type [Fe(NO)2(thiadiazole)] and new ruthenium complexes type trans-[RuCl4DMSO(thiadiazole)] where thiadiazole can be an anticancer agent. Those ligands can be readily replaced by GSTs aminoacid side chain groups, which lead to a synergism of inhibiting GST and releasing anticancer 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) eSNU-1 (ATCC CRL - 5971) and normal cell (ATCC - PCS-201-012) (AU)

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