A binuclear Fe(iii)/quinizarin complex as a structural model for anthracycline drugs binding to iron

• Autor(a) principal: Nascimento, Juliana Sales do
• Data de Publicação: 2022
• Outros Autores: Sousa, Aurideia Possidonio de, Gondim, Ana Claúdia Silva, Sousa, Eduardo Henrique Silva, Teixeira, Edson Holanda, Nascimento Neto, Luiz Gonzaga do, Bezerra, Beatriz Pinheiro, Ayala, Alejandro Pedro, Batista, Alzir Azevedo, Vasconcelos, Igor Frota de, Oliveira, Francisco Gilvane Sampaio de, Holanda, Alda Karine Medeiros
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da Universidade Federal do Ceará (UFC)
• Texto Completo: http://www.repositorio.ufc.br/handle/riufc/67284
• topic: Binuclear Fe(iii)/quinizarin complex; Anthracyclines; X-Ray diffraction

The cis-[Fe(cyclam)Cl2]Cl (cyclam = 1,4,8,11-tetraazacyclotetradecane) complex reacts with quinizarin (1,4-dihydroxy-9,10-anthraquinone, Qz), a biologically relevant molecule, yielding the binuclear complex [(Fe(cyclam))2(Qz)]Cl(PF6)3. This new compound was characterized by means of elemental analysis, X-ray diffraction, cyclic voltammetry and spectroscopic techniques. Crystallographic and FTIR data indicated that the bridging ligand, quinizarin, is coordinated to the FeIII cation via the oxygen atoms of the carbonyl groups in the form of quinones. The effect of ancillary (cyclam) and bridging (Qz) ligands on the properties of the complex is reflected by the stabilization of the FeIII–FeIII configuration supported by Mo¨ssbauer spectroscopy. The efficiency of ROS generation and DNA cleavage activity for this binuclear complex, as well as for the free quinizarin ligand, were investigated. This metal complex exhibited very low photochemical activity; however, it revealed a great ability to cleave the DNA molecule in the presence of glutathione, which was associated with the production of ROS species. Thereafter, the cytotoxic activity of these compounds was evaluated using the MTS assay against human tumor cells, namely lung adenocarcinoma (A549) and prostate carcinoma (LNCaP clone FGC), and against normal fibroblasts (L929). Our findings indicated low cytotoxic effects in general, where only a slight reduction in A549 and L929 cell viability was observed after light irradiation. Despite the lack of any significant biological activity, this binuclear compound validates in vitro the essential role of metal binding to an anthracycline-like moiety in the generation of ROS. The latter may be responsible for some of the cardiotoxicity reported for anthracycline-based drugs.