Dinitrosyl iron complexes containing thiadiazole or thiosemicarbazone derived from cinnamaldehyde: synthesis, characterization and potential antitumor application

Author(s)

Renan Diego Zanetti

• Document type: Master's Dissertation
• Press: Araraquara. 2018-03-20.
• Institution: Universidade Estadual Paulista (Unesp). Instituto de Química. Araraquara
• Defense date: 2018-02-27
• Advisor: José Clayston Melo Pereira

Abstract

Cancer is currently one of the leading causes of death in the world. In addition, increased cellular resistance to the form of treatment using radiation therapy with drug use has been observed. The enzymatic system glutathione S transferases (GSTs), one of the responsible for this resistance, catalyzes the conjugation of glutathione with cisplatin, which is one of the drugs most applied in cancer therapy, restricting its action. In this context, has been proposed the use of iron dinitrosyls (DNIC - dinitrosyl iron complex) [(Fe (NO ) 2 Ligand ] as an alternative to decrease the cellular resistance to antineopl astic agents. DNICs are generally formed in cells exposed to nitric oxide (NO) and bind to the enzymes of the GST f amily inhibiting their effect against anticancer drugs. Thus, it was proposed t o develop complexes of type [Fe(NO) 2 X] (X = thiosemicarbazone), where X would be a ligand with potential antineoplastic activity. These linkers would be readily substituted by GSTs amino acid side chain groups, providing a possible synergism of enzyme inhibition and release of antineoplastic agents. Thiosemicarbazones were synthesized from cinnamaldehyde and corresponding thiosemicarbazides in ethanolic medium and characterized by absorption spectroscopy in the infrared (IR), UV - Vis region, ¹H and ¹ ³C nuclear magnetic resonance (NMR), mass sp ectrometry and elemental analysis , as well as their tested cyclization products. The complexes were obtained from the pr eviously prepared precursor [Fe(CO) 2 (NO) 2 ] and the thiosemicarbazones, in tetrahydrofuran (THF) and characterized by absorption spectros copy in the infrared (IR) r egion molar conductance and mass spectrometry (MS). (AU)

• FAPESP's process: 16/04329-5 - Dinitrosyl complexes containing tiosemicarbazone, semicarbazone, tiadiazol or oxadiazole: synthesis, characterization and treatment against cancer
• Grantee: Renan Diego Zanetti
• Support Opportunities: Scholarships in Brazil - Master