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- Title
Chiral ruthenium(II) anthraquinone complexes as dual inhibitors of topoisomerases I and II.
- Authors
Kou, Jun-Feng; Qian, Chen; Wang, Jin-Quan; Chen, Xiang; Wang, Li-Li; Chao, Hui; Ji, Liang-Nian
- Abstract
DNA topoisomerases (I and II) have been one of the excellent targets in anticancer drug development. Here two chiral ruthenium(II) anthraquinone complexes, Δ- and Λ-[Ru(bpy)(ipad)], where bpy is 2,2′-bipyridine and ipad is 2-(anthracene-9,10-dione-2-yl)imidazo[4,5-f][1,10]phenanthroline, were synthesized and characterized. As expected, both of the Ru(II) complexes intercalate into DNA base pairs and possess an obviously greater affinity with DNA. Topoisomerase inhibition and DNA strand passage assay confirmed that the two complexes are efficient dual inhibitors of topoisomerases I and II by interference with the DNA religation. In MTT cytotoxicity studies, two Ru(II) complexes exhibited antitumor activity against HeLa, MCF-7, HepG2 and BEL-7402 tumor cell lines. Flow cytometry analysis shows an increase in the percentage of cells with apoptotic morphological features in the sub-G1 phase for Ru(II) complexes. Nuclear chromatin cleavage has also been observed from AO/EB staining assay and alkaline single-cell gel electrophoresis (comet assay). The results demonstrated that Δ- and Λ-[Ru(bpy)(ipad)] act as dual inhibitors of topoisomerases I and II, and cause DNA damage that can lead to cell cycle arrest and/or cell death by apoptosis. Graphical abstract: Chiral ruthenium(II) anthraquinone complexes Δ- and Λ-[Ru(bpy)(ipad)] are demonstrated to be efficient dual inhibitors of topoisomerases I and II, and cause DNA damage that can lead to cell cycle arrest and/or cell death by apoptosis.[Figure not available: see fulltext.]
- Subjects
METAL complexes; ORGANORUTHENIUM compounds; CHIRALITY; ANTHRAQUINONES; DNA topoisomerases; ENZYME inhibitors; ANTINEOPLASTIC agents; DRUG development
- Publication
Journal of Biological Inorganic Chemistry (JBIC), 2012, Vol 17, Issue 1, p81
- ISSN
0949-8257
- Publication type
Article
- DOI
10.1007/s00775-011-0831-6