Synthesis, characterization, DNA/BSA interactions and anticancer activity of achiral and chiral copper complexes

Abstract

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.

Cu(II), Ni(II) complexes derived from chiral Schiff-base ligands: Synthesis, characterization, cytotoxicity, protein and DNA–binding properties

“…Therefore, many novel metal complexes have been investigated and screened, and some of them are already in clinical trials [3,4]. Indeed, the cytotoxicity effect of metal complexes-mediated is generally accepted to result from their binding and cutting interaction with DNA, which leads to cell cycle arrest, apoptosis and the regeneration of cancers' DNA [5,6]. Even though the mechanism of antitumor activity exist diverse signaling pathways, DNA is the primary intracellular target of anticancer drugs, so the interaction between small molecules and DNA can often cause DNA damage in cancer cells, blocking the division of cancer cells [7][8][9].…”

Chirality‐Induced Variation in Interaction of Two Similar Copper(II) Coordination Polymers with Calf Thymus DNA: Exploration of Their Antimicrobial Activity and Cytotoxicity

“…As complex 1 is chiral (complex 1 crystallizes in chiral space group) and complex 2 is achiral, it may be concluded that the chirality of complex 1 played very significant role to binding of chiral DNA molecule. It could also be found in literature that when two complexes were otherwise similar structurally, a chiral complex had a greater affinity for DNA …”

Preparation, characterization and biological evaluation of two chiral binuclear copper(II) complexes

“…The exact methods and parameters of X‐ray crystallography used for the measurements of the structures are similar to our reported article . Single‐crystal X‐ray diffraction data of complexes 1 and 2 were collected at 113(2) K on a Bruker Smart 1000 CCD diffractometer using Mo‐Kα radiation (λ = 0.71073 Å) with the ω scan technique.…”

“…Besides the selection of metal centers, the rational design of ligands is also crucial for the metal‐based antitumor agents. In this case, polyquinoline‐based ligands have gained extensive attentions, their complexes have been widely studied and showed superior DNA affinity and biological activity . This is partly due to the N atoms in quinoline moieties serving as coordination sites can stabilize metal ions at various valence states.…”