New ruthenium polypyridyl complexes functionalized with fluorine atom or furan: Synthesis, DNA-binding, cytotoxicity and antitumor mechanism studies

• Published in: Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy Molecular and biomolecular spectroscopy, 2020-02, Vol.227, p.117534, Article 117534
• Main Authors: Jiang, Guang-Bin, Zhang, Wen-Yao, He, Miao, Gu, Yi-Ying, Bai, Lan, Wang, Yang-Jie, Yi, Qiao-Yan, Du, Fan
• Format: Article
• Language: English
• Subjects: Antitumor; Cell cycle arrest; DNA binding; Reactive oxygen species; Ru(II) polypyridyl complex
• ISSN: 1386-1425
• DOI: 10.1016/j.saa.2019.117534

Two novel ruthenium(II) polypyridyl complexes, namely, [Ru(dmp)2(CAPIP)](ClO4)2 (Ru(II)-1) and [Ru(dmp)2(CFPIP)](ClO4)2 (Ru(II)-2), which respectively contain (E)-2-(2-(furan-2-yl)vinyl)-1H-imidazo[4,5-f][1,10]phen-anthroline (CAPIP) and (E)-2-(4-fluorostyryl)-1H-imidazo[4,5-f][1,10]phenanthroline. (CFPIP), were first designed and characterized (dmp = 2,9-dimethyl-1,10-phenanthroline). DNA binding experiments indicated that Ru(II) complexes interact with CT DNA through intercalative mode. In addition, the complexes Ru(II)-1 and Ru(II)-2, showed remarkable cell cytotoxicity, giving the respective IC50 values of 4.1 ± 1.4 μM and 6.1 ± 1.4 μM on the A549 cancer cells. These values indicated higher activity than CAPIP, CFPIP, cisplatin (8.2 ± 1.4 μM) and other corresponding Ru(II) polypyridyl complexes. Furthermore, the Ru(II) complexes could arrive the cytoplasm through the cell membrane and accumulate in the mitochondria. Significantly, complexes Ru(II)-1 and Ru(II)-2 induced A549 cells apoptosis was mediated by increase of ROS levels and dysfunction of mitochondria, and resulted in cell cycle arrest and increased anti-migration activity on A549 cells. Overall, these results indicated that complexes Ru(II)-1 and Ru(II)-2 could be suitable candidates for further investigation as a chemotherapeutic agent in the treatment of tumors. DNA-binding behaviors of the Ru(II) complexes were studied. Antitumor activity of the Ru(II)-1 and Ru(II)-2 were assessed by MTT method. In addition, the antitumor activity in vitro, morphological changes, mitochondrial membrane potentials, ROS levels, cellular localization, cell invasion, apoptosis, and cell cycle arrest were investigated. [Display omitted] •Two new ruthenium(II) complexes were synthesized and characterized.•DNA-binding behaviors of the Ru(II) complexes were investigated.•The Ru(II) complexes displays high cytotoxic activity against A549 cells.•The complexes can induce apoptosis and increase intracellular ROS levels.•The mitochondrial membrane potential, cell cycle arrest and cell invasion were investigated.