Title
Structure and biological properties of mixed-ligand Cu(II) Schiff base complexes as potential anticancer agents
Author
Yi Gou, Jinlong Li, Boyi Fan, Bohui Xu, Min Zhou, Feng Yang
Year
2017
Journal
European Journal of Medicinal Chemistry
Abstract
We synthesized two mixed-ligand Cu(II) complexes containing different aroylhydrazone ligands and a pyridine co-ligand, namely, [Cu(L1)(Py)] (C1) and [Cu(L2)(Py)(Br)] (C2) (L1 = (E)-2-hydroxy-N′-((2-hydroxynaphthalen-1-yl)methylene)benzohydrazide, Py = pyridine, L2 = (E)-2-hydroxy-N′-(phenyl(pyridin-2-yl)methylene)benzohydrazide), and assessed their chemical and biological properties to understand their marked activity. C2 showed better anticancer activity than C1 in various human cancer cell lines, including the cisplatin-resistant lung cancer cell line A549cisR. Both Cu(II) complexes, especially C2, displayed promising anti-metastatic activity against HepG2 cells. Spectroscopic titration and agarose gel electrophoresis experiments indicated that C2 exhibited binding affinity toward calf-thymus DNA and efficient pBR322 DNA-cleaving ability. Further mechanistic studies showed that C2 effectively induced DNA damage and thus led to cell cycle arrest at the G2/M phase, and also stimulated mitochondrial dysfunction mediated by reactive oxygen species and caspase-dependent apoptosis.
Instrument
J-810
Keywords
Circular dichroism, DNA structure, Ligand binding, Biochemistry, Medicinal