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

• Published in: New journal of chemistry Vol. 46; no. 12; pp. 5515 - 5525
• Main Authors: do Nascimento, Juliana S, de Sousa, Aurideia P, Gondim, Ana C. S, Sousa, Eduardo H. S, Teixeira, Edson H, do Nascimento Neto, Luiz Gonzaga, Bezerra, Beatriz Pinheiro, Ayala, Alejandro Pedro, Batista, Alzir A, Vasconcelos, Igor F, Oliveira, Francisco G. S, Holanda, Alda K. M
• Format: Journal Article
• Language: English
• Published: Cambridge Royal Society of Chemistry 21.03.2022
• Subjects: Anthraquinones; Binding; Biological activity; Carbonyl groups; Carbonyls; Coordination compounds; Crystallography; Cytotoxicity; Drugs; Fibroblasts; Glutathione; Iron; Ligands; Light irradiation; Mossbauer spectroscopy; Oxygen atoms; Quinones; Structural models
• ISSN: 1144-0546; 1369-9261
• DOI: 10.1039/d1nj04087a

The cis -[Fe(cyclam)Cl 2 ]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(PF 6 ) 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 Fe III 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 Fe III -Fe III configuration supported by Mössbauer 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. Quinizarin, an anthracyclin-like compound, was used to prepare a binuclear complex, [(Fe(cyclam)) 2 Qz]Cl(PF 6 ) 3 , which showed damage to DNA with glutathione. This mimic of anthracyclin drugs might explain undesired side effects of these compounds.