Novel lawsone-containing ruthenium(II) complexes: Synthesis, characterization and anticancer activity on 2D and 3D spheroid models of prostate cancer cells

Autor(es)

De Grandis, Rone Aparecido ^[1] ; da Silva dos Santos, Patrick Wellington ^[2] ; de Oliveira, Katia Mara ^[3] ; Tomazela Machado, Ana Rita ^[2] ; Aissa, Alexandre Ferro ^[2] ; Batista, Alzir Azevedo ^[3] ; Greggi Antunes, Lusania Maria ^[2] ; Pavan, Fernando Rogerio ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ, Sch Pharmaceut Sci, BR-14800903 Araraquara, SP - Brazil

^[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil

^[3] Univ Fed Sao Carlos, Dept Chem, BR-13561901 Sao Carlos, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BIOORGANIC CHEMISTRY; v. 85, p. 455-468, APR 2019.
• Citações Web of Science: 3

Resumo

This study describes a series of newly synthesized phosphine/diimine ruthenium complexes containing the lawsone as bioligand with enhanced cytotoxicity against different cancer cells, and apoptosis induction in prostatic cancer cells DU-145. The complexes {[}Ru(law)(N-N)(2)]PF6 where N-N is 2,2'-bipyridine (1) or 1,10-phenanthroline (2) and {[}Ru(law)(dppm)(N-N)]PF6, where dppm means bis(diphenylphosphino)methane, N-N is 2,2'-bipyridine (3) or 1,10-phenanthroline (4), and law is lawsone, were synthesized and fully characterized by elemental analysis, molar conductivity, NMR, UV-vis, IR spectroscopies and cyclic voltammetry. The interaction of the complexes (1-4) with DNA was evaluated by circular dichroism, gel electrophoresis, and fluorescence, and the complexes presented interactions by the minor grooves DNA. The phosphinic series of complexes exhibited a remarkably broad spectrum of anticancer activity with approximately 34-fold higher than cisplatin and 5-fold higher than doxorubicin, inhibiting the growth of 3D tumor spheroids and the ability to retain the colony survival of DU-145 cells. Also, the complex (4) inhibits DU-145 cell adhesion and migration potential indicating antimetastatic properties. The mechanism of its anticancer activity was found to be related to increased reactive oxygen species (ROS) generation, increased the BAX/BCL-2 ratio and subsequent apoptosis induction. Overall, these findings suggested that the complex (4) could be a promising candidate for further evaluation as a chemotherapeutic agent in the prostate cancer treatment. (AU)

• Processo FAPESP: 18/00163-0 - Desenvolvimento e busca de novos antimicrobianos contra Tuberculose: da triagem a estudos pré-clínicos in vivo
• Beneficiário: Fernando Rogério Pavan
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/22429-7 - Avaliação toxicogenética e estudo dos mecanismos de resposta antiproliferativa de metalofármacos de rutênio contendo bioligantes naftoquinônicos em modelos celulares tumorais convencionais e em 3D
• Beneficiário: Rone Aparecido de Grandis
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 16/16312-0 - Citotoxidade e mecanismo de ação de complexos de rutênio contendo produtos naturais ou derivados
• Beneficiário: Alzir Azevedo Batista
• Modalidade de apoio: Auxílio à Pesquisa - Regular