Cyclopalladated compounds containing 2,6-lutidine: Synthesis, spectral and biological studies

Autor(es):Mostrar menos -

da Cunha, Gislaine A. ^[1] ; de Souza, Ronan F. F. ^[1] ; de Farias, Renan L. ^[1] ; Moreira, Mariete B. ^[1] ; Silva, Debora E. S. ^[1] ; Zanetti, Renan D. ^[1] ; Garcia, Daniel M. ^[2] ; Spindola, Daniel G. ^[2] ; Michelin, Luis F. G. ^[2] ; Bincoletto, Claudia ^[2] ; de Souza, Aline A. ^[3] ; Antunes, Alyne A. ^[3] ; Judice, Wagner A. de S. ^[3] ; Leitao, Renan C. F. ^[4] ; Deflon, Victor M. ^[4] ; Mauro, Antonio E. ^[1] ; Netto, Adelino V. G. ^[1]

Afiliação do(s) autor(es)

^[1] UNESP Univ Estadual Paulista, Inst Chem, BR-14800060 Araraquara, SP - Brazil

^[2] Sao Paulo Fed Univ UNIFESP, Dept Pharmacol, Sao Paulo Med Sch, BR-04044020 Sao Paulo, SP - Brazil

^[3] Univ Mogi das Cruzes, CIIB, Av Candido Xavier de Almeida Souza 200, CP 411, BR-08701970 Mogi Das Cruzes, SP - Brazil

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

• Tipo de documento: Artigo Científico
• Fonte: Journal of Inorganic Biochemistry; v. 203, FEB 2020.
• Citações Web of Science: 4

Resumo

Bridge splitting reactions between {[}Pd(C-2,N-dmba)(mu-X)](2) (dmba = N,N-dimethylbenzylamine; X = Cl, I, N-3, NCO) and 2,6-lutidine (lut) in the 1:2 molar ratio at room temperature afforded cyclopalladated compounds of general formulae {[}Pd(C-2,N-dmba)(X)(lut)] [X = Cl- (1), I-(2), NNN-(3), NCO-(4)], which were characterized by elemental analyses and infrared (IR), H-1 NMR spectroscopy. The molecular structures of all synthesized palladacycles have been solved by single-crystal X-ray crystallography. The cytotoxicity of the cyclopalladated compounds has been evaluated against a panel of murine [mammary carcinoma (4T1) and melanoma (B16F10-Nex2)] and human [melanoma (A2058, SK-MEL-110 and SK-MEL-5) tumor cell lines. All complexes were about 10 to 100-fold more active than cisplatin, depending on the tested tumor cell line. For comparison purposes, the cytotoxic effects of 1-4 towards human lung fibroblasts (MRC-5) have also been tested. The late apoptosis-inducing properties of 1-4 compounds in SK-MEL-5 cells were verified 24 h incubation using annexin V-Fluorescein isothiocyanate (FITC)/propidium iodide (PI). The binding properties of the model compound 1 on human serum albumin (USA) and calf thymus DNA (ct-DNA) have been studied using circular dichroism and fluorescence spectroscopy. Docking simulations have been carried out to gain more information about the interaction of the palladacycle and HSA. The ability of compounds 1-4 to inhibit the activity of cathepsin B and L has also been investigated in this work. (AU)

• Processo FAPESP: 12/15486-3 - Compostos de Pd(II): síntese, citotoxicidade e investigação espectrofotométrica da interação com o DNA
• Beneficiário: Regina Celia Galvao Frem
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/02205-1 - Estudo do comportamento cinético das convertases
• Beneficiário: Wagner Alves de Souza Júdice
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 09/54011-8 - EMU: aquisição de difratômetro de raios X de monocristal para análise estrutural de moléculas pequenas e proteínas
• Beneficiário: Victor Marcelo Deflon
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 16/25112-4 - Avaliação de moduladores da atividade de proteases envolvidas em processos patológicos
• Beneficiário: Wagner Alves de Souza Júdice
• Modalidade de apoio: Auxílio à Pesquisa - Regular