Journal
POLYHEDRON
Volume 179, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.poly.2020.114369
Keywords
Benzimidazole-quinoline derivative; Pt(II) and Cu(II) compounds; DNA interaction; Apoptosis; Anticancer
Categories
Funding
- National Natural Science Foundation of China [21371046, 21401041]
- Key Scientific Research Project Plan of Colleges and Universities in He'nan Province [19A150017]
- Funding Program for Academic Technology Leaders of the He'nan University of Urban Construction [YCJXSJSDTR201705]
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In this study, three transition metal compounds based on benzimidazole-quinoline ligand [Cu(pbmq)Cl-2](2) (1), [Cu(pbmq)Br-2](2) (2), and Pt(pbmq)Cl-2 (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. (C) 2020 Elsevier Ltd. All rights reserved.
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