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Transition metal compounds bearinhg thiosemicarbazones and phosphines as ligand: investigation of cytotoxicity and mechanism of action


The main objective of this project is the design of new thiosemicarbazones and their transition metal complexes which act as dual inhibitors of DNA topoisomerase II ± and cathepsin B. The anticancer activity of the compounds will be evaluated by MTT assays against the normal and tumor cells. Also, will be carried out the apoptosis assays. The interaction between the compounds and topoisomerase will be evaluated by agarose gel electrophoresis assay. The potency of inhibition of cathepsin B activity of the complexes will be assayed by fluorometirc experiments. To better understand the mechanism of action of these compounds against the target enzyme, molecular docking studies could be performed. The thiosemicarbazones will be synthesized starting from suitable aldehydes/cetones and thiossemicarbazides. The complexes will be obtained by the reactions of the appropriated metallic salt and the thiossemicarbazones. Phosphines and halogens or pseudohalides groups will act as co-ligands. 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. (AU)

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Scientific publications (4)
(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)
LIMA, MAURO ALMEIDA; COSTA, VINICIUS A.; FRANCO, MARIANE ARALIJO; DE OLIVEIRA, GABRIELA P.; DEFLON, VICTOR M.; ROCHA, FILLIPE VIEIRA. Palladium(II) complexes bearing thiosemicarbazone and phosphines as inhibitors of DNA-Topoisomerase II enzyme: Synthesis, characterizations and biological studies. Inorganic Chemistry Communications, v. 112, . (16/04201-9, 19/11242-1)
CORDEIRO, PAULO JORGE MARQUES; MARTINS, ALYSSON STEFAN; PEREIRA, GEORGE BUENO SANTANA; ROCHA, FILLIPE VIEIRA; RODRIGO, MANUEL ANDRES RODRIGO; LANZA, MARCOS ROBERTO DE VASCONCELOS. High-performance gas-diffusion electrodes for H2O2 electrosynthesis. Electrochimica Acta, v. 430, p. 11-pg., . (14/50945-4, 19/11242-1, 16/04201-9, 17/10118-0, 20/13088-7, 17/13123-4, 16/19612-4, 16/01937-4)
ROCHA, FILLIPE V.; FARIAS, RENAN L.; LIMA, MAURO A.; BATISTA, VICTOR S.; NASCIMENTO-JUNIOR, NAILTON M.; GARRIDO, SAULO S.; LEOPOLDINO, ANDREA M.; GOTO, RENATA N.; OLIVEIRA, ADRIANO B.; BECK, JOHANNES; et al. Computational studies, design and synthesis of Pd(II)-based complexes: Allosteric inhibitors of the Human Topoisomerase-II alpha. Journal of Inorganic Biochemistry, v. 199, . (12/15486-3, 16/17711-5, 13/20156-5, 16/04201-9)
MARQUES CORDEIRO-JUNIOR, PAULO JORGE; MARTINS, ALYSSON STEFAN; SANTANA PEREIRA, GEORGE BUENO; ROCHA, FILLIPE VIEIRA; RODRIGO RODRIGO, MANUEL ANDRES; DE VASCONCELOS LANZA, MARCOS ROBERTO. Bisphenol-S removal via photoelectro-fenton/H2O2 process using Co-porphyrin/Printex L6 gas diffusion electrode. Separation and Purification Technology, v. 285, p. 13-pg., . (20/13088-7, 19/11242-1, 17/10118-0, 16/04201-9, 14/50945-4, 16/01937-4, 17/13123-4, 16/19612-4)

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