Mixed-ligand mononuclear copper(II) complex: crystal structure and anticancer activity.
A novel copper(II) complex with mixed ligands including β-[(3-formyl-5-methyl-2-hydroxy-benzylidene)amino]propionic acid anion and 1,10'-phenanthroline was synthesized, and its crystal structure was thoroughly characterized. It exerted excellent inducing apoptosis, anti-angiogenesis and antiproliferative properties in vitro. The complex can bind human serum albumin (HSA) at physiological pH conditions. Remarkably, it can induce formation of the mixed parallel/antiparallel G-quadruplex structures in the G-rich sequence of the proximal vascular endothelial growth factor (VEGF) promoter, and stabilize these G-quadruplex structures, which provide an opportunity for anti-angiogenesis chemotherapeutics. Furthermore, the complex showed a strong uptake, and exhibited multiple anticancer functions by inhibiting the expression of p-Akt and p-Erk1/2 proteins and by upregulating the levels of reactive oxygen species (ROS). Because of the reported results, this new copper(II) complex qualifies itself as a potential anticancer drug candidate.
Department of Chemistry, Jinan University, Guangzhou 510632, China; College of Pharmacy, Guilin Medical University, Guilin 541004 (China).
Xiu-Ying
XY
Qin
Ya-Nan
YN
Liu
Qian-Qian
QQ
Yu
Li-Cong
LC
Yang
Ying
Y
Liu
Yan-Hui
YH
Zhou
Jie
J
Liu
D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D056831:Coordination Complexes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D054856:G-Quadruplexes; D006367:HeLa Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D008968:Molecular Conformation; D010618:Phenanthrolines / Q000737:chemistry; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D056831:Coordination Complexes; D008024:Ligands; D010618:Phenanthrolines; D017382:Reactive Oxygen Species; D012709:Serum Albumin; D042461:Vascular Endothelial Growth Factor A; D003300:Copper; D051057:Proto-Oncogene Proteins c-akt
VEGF G-quadruplexes; anti-angiogenesis; antitumor agents; apoptosis; copper(II) complexes