Palladium(ii) complexes bearing 1-iminothiolate-3,5-dimethylpyrazoles: synthesis, cytotoxicity, DNA binding and enzymatic inhibition studies

Author(s):Show less -

de Moura, Thales Reggiani ^[1] ; Zanetti, Renan Diego ^[1] ; Silva, Debora Eduarda Soares ^[1] ; de Farias, Renan Lira ^[1] ; Mauro, Antonio Eduardo ^[1] ; Pereira, Jose Clayston Melo ^[1] ; de Souza, Aline Aparecida ^[2] ; da Silva Siqueira, Fabio ^[2] ; de Souza Judice, Wagner Alves ^[2] ; Lima, Mauro Almeida ^[3] ; Rocha, Fillipe Vieira ^[3] ; Deflon, Victor Marcelo ^[4] ; Vieira de Godoy Netto, Adelino ^[1]

Affiliation

^[1] UNESP Univ Estadual Paulista, Inst Quim, Dept Quim Geral & Inorgan, BR-14800060 Araraquara, SP - Brazil

^[2] UMC Univ Mogi das Cruzes, Ctr Interdisciplinar Invest Bioquim, BR-08701970 Mogi Das Cruzes, SP - Brazil

^[3] UFSCar Univ Fed Sao Carlos, Dept Quim, BR-13565905 Sao Carlos, SP - Brazil

^[4] Univ Sao Paulo, Inst Quim Sao Carlos, BR-13566590 Sao Carlos, SP - Brazil

• Document type: Journal article
• Source: NEW JOURNAL OF CHEMISTRY; v. 44, n. 45, p. 19891-19901, DEC 7 2020.
• Web of Science Citations: 0

Abstract

Four palladium(ii) compounds of general formulae {[}PdCl(L-n)(PPh3)] [L-1 = 3,5-dimethylpyrazole-1-iminothiolate (1); L-2 = 3,5-dimethyl-pyrazole-N-methyl-1-iminothiolate (2); L-3 = 3,5-dimethylpyrazole-N-ethyl-1-iminothiolate (3); L-4 = 3,5-dimethylpyrazole-N-phenyl-1-iminothiolate (4); and PPh3 = triphenylphosphine] have been synthesized. The novel synthesized compounds have been characterized by C, H and N elemental analysis, 1D (H-1 and C-13) and 2D (HSQC and HMBC) NMR, MS, FT-IR, and molar electrical conductivity measurements. The molecular structure of complex 3 has been solved by single-crystal X-ray crystallography. The stability of the complexes in solution was studied in a DMSO/D2O (7 : 3) solution after 48 h. The antiproliferative activity of all free ligands and the stable palladium complexes 2-4 was assayed using the human breast tumour cell line MCF-7, lung tumour cell line A549 and human fetal lung fibroblast cell line MRC-5. Complex 3 was more active than cisplatin against MCF-7 cells, whilst palladium compounds 2-4 exhibited no drug response towards A549 cells at concentrations 2 and 3 to ct-DNA have been studied using circular dichroism and fluorescence spectroscopy. The topoisomerase II alpha inhibition has been studied for complex 2 and 3. The ability of all complexes to inhibit the activity of cathepsin B and L has also been investigated in this work. Compound 4 inhibited more than 50% of the cathepsin B activity at a concentration of 10 mu M. Docking simulations have been carried out to gain more information about the interaction of the complexes and cathepsin B. (AU)

• FAPESP's process: 15/12098-0 - Dinitrosyl complexes containing thiol and/or thiosemicarbazone : synthesis, characterization and treatment against cancer
• Grantee: José Clayston Melo Pereira
• Support type: Regular Research Grants
• FAPESP's process: 16/25112-4 - Evaluation of modulators of the activity of proteases involved in pathological processes
• Grantee: Wagner Alves de Souza Júdice
• Support type: Regular Research Grants
• FAPESP's process: 14/02205-1 - Study of kinetic behavior of convertases
• Grantee: Wagner Alves de Souza Júdice
• Support type: Regular Research Grants
• FAPESP's process: 09/54011-8 - Acquisition of a single-crystal X-ray diffractometer for the structural analysis of small molecules and proteins
• Grantee: Victor Marcelo Deflon
• Support type: Multi-user Equipment Program
• FAPESP's process: 19/11242-1 - Relative quantification of DNA-Topoisomerases enzymes in cell lines: Correlation between cytotoxicity and mechanism of action of coordination compounds
• Grantee: Fillipe Vieira Rocha
• Support type: Regular Research Grants
• FAPESP's process: 16/17711-5 - INVESTIGATION OF THE ANTITUMOR POTENTIAL OF PALLADIUM(II) COMPOUNDS CONTAINING ORTHOMETALLATED OR N,S-DONOR LIGANDS
• Grantee: Adelino Vieira de Godoy Netto
• Support type: Regular Research Grants