Heteroleptic tris-chelate ruthenium(II) complexes of N,N-disubstituted-N `-acylthioureas: Synthesis, structural studies, cytotoxic activity and confocal microscopy studies

Autor(es)

Barolli, Joao P. ; Maia, Pedro I. S. ; Colina-Vegas, Legna ; Moreira, Jane ; Plutin, Ana M. ; Mocelo, Raul ; Deflon, Victor M. ; Cominetti, Marcia R. ; Camargo-Mathias, Maria I. ; Batista, Alzir A.

• Tipo de documento: Artigo Científico
• Fonte: Polyhedron; v. 126, p. 33-41, APR 18 2017.
• Citações Web of Science: 7

Resumo

Ruthenium complexes have been assessed as anti-tumor agents against cancer cells. In this project, new heteroleptic rutheniuM(II) complexes with general formulae {[}Ru(L)(bipy)(dppb)](PF6) (where L = N,N-disubstituted-N'-acylthiourea, bipy = 2,2'-bipyridine and dppb = 1,4-bis(diphenylphosphino)butane) were synthesized and characterized by elemental analysis, IR and NMR and (H-1 and P-31[H-1]) spectroscopies, molar conductivity measurements and single crystal X-ray diffractometry. The IR and NMR data suggest the coordination of the ligands to the Ru(II) metal center through the tfiiocarbonyl and carbonyl groups. The structures of the new complexes were further studied by X-ray crystallography, which confirmed the coordination of the ligands with the metal through the sulfur and oxygen atoms, leading to the formation of distorted octahedral complexes. The N,N-disubstituted-N'-acylthioureas and their complexes were screened with respect to their in vitro cytotoxicity. All compounds exhibited considerable antipro-liferative activity against MCF-7 (human breast tumor cells ATCC HTB-26), DU-145 (human prostate tumor cells ATCC HTB-26), and relatively low toxicity against fibroblast L929 cells (health cell line from mouse ATCC CCL-1). A preliminary study regarding the mechanism of action of these compounds by con focal microscopy shows alterations of the actin filaments leading to Modifications in cytoskeletal supporting the cell death and that the cell nucleus is not main target of these complexes. (C) 2017 Elsevier Ltd. All rights reserved. (AU)

• 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: 11/21033-9 - Efeito de inseticidas na espermatogênese das abelhas Apis mellifera (Linnaeus, 1758) e Scaptotrigona postica (Latreille, 1807) (Hymenoptrera: Apidae)
• Beneficiário: Jane Carla Soares Moreira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 11/16380-1 - Complexos de Au, Re e Tc com tiossemicarbazonas de interesse no desenvolvimento de fármacos ou radiofármacos para diagnóstico ou terapia
• Beneficiário: Pedro Ivo da Silva Maia
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/21611-8 - Complexos de rutênio(II) coordenados a dipiridofenazinas e dipiridoquinoxalinas: ensaios celulares em linhagens de células tumorais e estudo do mecanismo de ação visando sua aplicação em terapias anticâncer
• Beneficiário: João Paulo Barolli Reis
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado