Grant number: | 16/17711-5 |
Support Opportunities: | Regular Research Grants |
Start date: | December 01, 2016 |
End date: | November 30, 2018 |
Field of knowledge: | Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry |
Principal Investigator: | Adelino Vieira de Godoy Netto |
Grantee: | Adelino Vieira de Godoy Netto |
Host Institution: | Instituto de Química (IQ). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil |
Associated researchers: | Claudia Bincoletto Trindade ; Fernando Rogério Pavan ; Fillipe Vieira Rocha ; José Clayston Melo Pereira ; Marlus Chorilli ; Patrícia Bento da Silva |
Abstract
This project deals with the synthesis, characterization and evaluation of the antitumor potential of compounds [PdCl(C2,N-ox)(PR3)], [Pd2Cl2(C2,N-ox)2(µ-PP)] and [PdCl(CINTSC)(PR3)] (PR3 = tertiary monodentate phosphanes, PP = diphosphanes; ox = orthometallated oximes functionalized or not, CINTSC = thiosemicabazones derived from cinmaldehyde). The compounds will be characterized by elemental analysis, IR and NMR spectroscopies, ESI/MS mass spectrometry, thermogravimetry (TG) and single crystal X-ray diffraction methods. The cytotoxicity of the compounds towards normal and tumor cells together with their ability to inhibit toposiomerase IIa and catepsin B will be evaluated. The compounds with promising results will be further selected to studies about the involvement of the lysosomal mitochondrial axis in their respective mechanism of action. The induction potential of apoptosis/necrosis and cleavage of caspase-3 mediated by these selected compounds will be also evaluated. Aiming at improving solubility and selectivety, these Pd(II) compounds will be incorporated into nanostructured lipid systems, which will be characterized by dynamic light scattering, polarized light microscopy, zeta potential, rheological behavior and thermal analysis. In sillico studies will be carried out in order to gain more knowledge about the possible mechanism involved in inhibitory enzymatic activity induced by these complexes. (AU)
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