Palladium (II) complexes as inhibitors of cathepsin B and topoisomerase I beta: Synthesis, characterization, and cytotoxicity

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Akinyemi, Amos O. ; Pereira, George B. S. ; Oliveira, Gabriela P. ; Lima, Mauro A. ; Rocha, Josias S. ; Costa, Vinicius A. ; Fortaleza, Dario B. ; Teixeira, Tamara ; Zanotti, Karine ; Forim, Moacir Rossi ; Araujo-Neto, Joao H. ; Ellena, Javier ; Rocha, Fillipe Vieira

• Tipo de documento: Artigo Científico
• Fonte: Journal of Molecular Structure; v. 1294, p. 14-pg., 2023-12-15.

Resumo

This research presents the synthesis, characterization, anticancer activity, and investigation of biological targets of three new palladium (II) complexes. The compounds were characterized by spectroscopies techniques (UV-Vis, NMR, and IR), elemental analysis, mass spectrometry, and one for monocrystal X-ray diffraction. The cytotoxic activity of the complexes against two cell lines, A2780cis (cisplatin resistance ovarian tumor cell line) and MRC-5 (non-tumor lung cell), was evaluated. The in vitro cytotoxicity assays using the MTT method revealed a significant cytotoxic activity of the palladium complexes against the evaluated cell lines, highlighting the resistance tumor cell line, A2780cis. Also, DNA interaction studies suggested that the compounds either do not interact, or interact weakly with DNA via groove and/or electrostatically. The interaction assay demonstrated that the compounds can weakly to moderately bind to the HSA biomolecule through electrostatic or van der Waals forces. In addition, agarose gel electrophoresis assays indicated that the complexes could not inhibit the action of the enzyme, topoisomerase II alpha. Nonetheless, the complexes demonstrated a promising target against topoisomerase I beta by promoting its inhibition. Finally, fluorescence studies revealed the capacity of irreversible inhibition of the complexes against the enzyme, cathepsin B. 1,1-Diphenyl-2-picryl-hydrazyl (DPPH) antioxidant assay did not show significant scavenging of DPPH radical. The results showed that the proposed structural features generate compounds of high cytotoxicity that can inhibit the action of cathepsin B and topoisomerase I beta. (AU)

• Processo FAPESP: 19/11242-1 - Quantificação relativa de enzimas DNA-Topoisomerase em linhagens celulares: estreitamento da correlação citotoxicidade-mecanismo de ação de compostos de coordenação
• Beneficiário: Fillipe Vieira Rocha
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 21/04876-4 - Estudos sobre estrutura & atividade de complexos de RuII/areno/mercaptoligantes frente ao câncer
• Beneficiário: João Honorato de Araujo Neto
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 22/02876-0 - Avaliação do perfil biológico de complexos de coordenação: uma abordagem em modelos celulares 2D e 3D
• Beneficiário: Fillipe Vieira Rocha
• Modalidade de apoio: Auxílio à Pesquisa - Regular