Synthesis, characterization, DNA/BSA interactions and anticancer activity of achiral and chiral copper complexes.
Six novel copper(ii) complexes of [CuCl]ClO4 (), [Cu(acac)]PF6 (), [CuCl]2(PF6)2 (), [CuCl]2(PF6)2 (), [Cu(acac)]PF6 () and [Cu(acac)]PF6 (), ( = 1-naphthyl-N,N-[bis(2-pyridyl)methyl]amine, = R/S-1-naphthyl-N,N-[bis(2-pyridyl)methyl]ethanamine, acac = diacetone) were synthesized to serve as artificial nucleases. All complexes were structurally characterized using X-ray crystallography. The crystal structures showed the presence of distorted square-planar CuLCl (, and ) and distorted tetragonal-pyramidal CuL(acac) (, and ) geometry. The interaction of these complexes with calf thymus DNA (CT-DNA) was researched by means of several spectroscopy methods, which indicated that the complexes were bound to CT-DNA by an intercalation binding mode. DNA cleavage experiments revealed that the complexes exhibited remarkable DNA cleavage activities in the presence of H2O2, and single oxygen ((1)O2) or hydroxyl radicals may serve as the major cleavage active species. In particular, the in vitro cytotoxicity of the complexes on four human cancer cell lines (HeLa, MCF-7, Bel-7404 and HepG-2) demonstrated that the six compounds had broad-spectrum anti-cancer activity with low IC50 values. The stronger cytotoxicity and DNA cleavage activity of the chiral enantiomers compared with chiral analogues verified the influence of chirality on the antitumor activity of complexes. Meanwhile, the protein binding ability was revealed by quenching of tryptophan emission with the addition of complexes using BSA as a model protein. The results indicated that the quenching mechanism of BSA by the complexes was a static process.
College of Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China. tiant@nankai.edu.cn.
Xue-Quan
XQ
Zhou
Qian
Q
Sun
Lin
L
Jiang
Si-Tong
ST
Li
Wen
W
Gu
Jin-Lei
JL
Tian
Xin
X
Liu
Shi-Ping
SP
Yan
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002417:Cattle; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D053837:DNA Cleavage / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D012710:Serum Albumin, Bovine / Q000378:metabolism*; D013237:Stereoisomerism
D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D012710:Serum Albumin, Bovine; D003300:Copper; D004247:DNA