Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 114, Issue -, Pages 244-256Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2016.02.055
Keywords
Copper complexes; Chirality; Crystal structure; Anticancer ability; Apoptosis mechanism
Categories
Funding
- National Natural Science Foundation of China [21171101, 21071083, 21471085]
- MOE Innovation Team of China [IRT13022]
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Four copper(II) complexes with chiral Schiff-base ligands, [Cu(R-L-1)(2)]center dot EtOAc (1) and [Cu(S-L-1)(2)]center dot EtOAc (2), [Cu(R-L-2)(2)]center dot EtOAc (3) and [Cu(S-L-2)(2)]center dot EtOAc (4), (R/S-HL1 = (R/S)-(1-naththyl)-salicylaldimine, R/S-HL2 = (R/S)-(1-naththyl)-3-methoxysalicylaldimine, EtOAc = ethyl acetate) were synthesized to serve as artificial nucleases and anticancer drugs. All complexes and R/S-HL1 ligands were structurally characterized by X-ray crystallography. The interaction of these complexes with CT-DNA was researched via several spectroscopy methods, which indicates that complexes bind to CT-DNA by moderate intercalation binding mode. Moreover, DNA cleavage experiments revealed that the complexes exhibited remarkable DNA cleavage activities in the presence of H2O2 via the generation of hydroxyl radical. Particularly, complex 4 also could nick DNA with the production of O-1(2). And all complexes exhibited excellent cytotoxicity to MDA-MB-231, A549 and Hela human cancer cells in micromole magnitude. Furthermore, complex 4 exhibited comparable cytotoxic effect to cisplatin against the proliferation of MDA-MB-231 and A549 cancer cells, as well as showed better anticancer ability to the three cancer cells than the other complexes. The results of cell cycle analysis indicated that complexes 3-4 could induce G(2)/M phase cell cycle arrest. Furthermore, MDA-MB-231 cells treated with 3 and 4 were subjected to apoptosis and death by generation of ROS and the activation of caspase-3. Interestingly, the chiral complexes 3 and 4 may induce cell apoptosis through extrinsic and mitochondrial intrinsic pathway, respectively. (C) 2016 Elsevier Masson SAS. All rights reserved.
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