Crystal structure, DNA interaction and in vitro anticancer activity of Cu(II) and Pt(II) compounds based on benzimidazole-quinoline derivative. (15th March 2020)

• Record Type: Journal Article
• Authors: Li, Sen; Zhao, Jin'an; Yuan, Bangpeng; Wang, Xinyang; Zhang, Junshuai; Yue, Liang; Hou, Hongwei; Hu, Jiyong; Chen, Shufang
• Is Part Of: Polyhedron. Volume 179(2020)
• Publication Date: 2020-03-15
• Subjects: Benzimidazole-quinoline derivative -- Pt(II) and Cu(II) compounds -- DNA interaction -- Apoptosis -- Anticancer; Chemistry, Inorganic -- Periodicals; Chimie inorganique -- Périodiques; Organometaalverbindingen; Anorganische chemie; 546.05
• DOI: 10.1016/j.poly.2020.114369
• Languages: English
• ISSNs: 0277-5387

Abstract

Graphical abstract: Compound 1 with bimetallic structure interacts with DNA by intercalation and exhibits cleavage activity to DNA, causing apoptosis of SMMC7721 cells via intrinsic mitochondrial pathway. Abstract: In this study, three transition metal compounds based on benzimidazole-quinoline ligand [Cu(pbmq)Cl2 ]2 (1), [Cu(pbmq)Br2 ]2 (2), and Pt(pbmq)Cl2 (3) (where pbmq = 2-((2-(pyridin-2-yl)-1H-benzo[ d ]imidazol-1-yl)methyl)quinolone), were synthesized and characterized. The compounds showed much higher cytotoxicity than pbmq against the tested human cancer cell lines. Notably, compound 1 exhibited marked anticancer activity against SMMC7721 cells. Hence, compound 1 was selected for further studies to understand the underlying mechanisms of its anticancer activity. Fluorescence, CD spectroscopy studies and viscosity determination showed that compound 1 could strongly bind to calf thymus DNA (CT-DNA). The CT-DNA binding properties revealed that intercalation might be the most probable binding mode. Moreover, compound 1 exhibited DNA cleavage activity. Cell uptake implied that compound 1 could enter the cells and accumulate mainly in the nucleus. Besides, flow cytometry analysis indicated that compound 1 could induce cycle arrest and apoptosis in SMMC7721 cells. Further experiments confirmed that compound 1 triggered apoptosis in SMMC7721 cells via the intrinsic mitochondrial pathway.