Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 70, Issue -, Pages 640-648Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2013.10.031
Keywords
Isoquinoline; Copper(II) complexes; Synthesis; Crystal structure; Cytotoxicity
Categories
Funding
- National Natural Science Foundation of China [21271051]
- National Basic Research Program of China [2012CB723501]
- Natural Science Foundation of Guangxi Province [2012GXNSFDA385001, 2012GXNSFDA053005]
- BAGUI Scholar program of Guangxi, China
- [IRT1225]
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Three new copper(II) complexes of 5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline (PYP), i.e. [Cu-2(PYP)(2)Cl-4] (1), [Cu-4(PYP)(4)(ClO4)(2)(H2O)(2)](ClO4)(2)center dot 2H(2)O (2), and [Cu-2(PYP)(2)Cl-4](n) (3), were synthesized and fully characterized. In comparison to free PYP, complexes 1-3 exhibited enhanced cytotoxicity against tested human tumor cell lines BEL-7404, SK-OV-3, A549, A375, MGC-803 and NCI-H460, with IC50 values ranging from 0.31 to 30.76 mu M. Complexes 1-3 exhibited lower cytotoxicity to HL-7702 than them to cancer cells. Complex 1 induced apoptotic death of BEL-7404, which involved mitochondria in the process. Caspase-3 activation assay indicated that 1 could be an efficient activator of caspase-3. DNA binding studies by UV-vis, DNA-melting, competitive binding, CD, viscosity measurement and agarose gel electrophoresis, revealed that intercalation might be the most likely binding mode of 1 with DNA. (C) 2013 Elsevier Masson SAS. All rights reserved.
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