Chiral copper(II) complex based on natural product rosin derivative as promising antitumour agent

• The copper (II) complex shows stronger binding affinity to DNA compared with the ligand.
• The binding mode between the complex and DNA is intercalation.
• The in vitro cytotoxicity of the complex was stronger than the ligand.
• Our work provides a rationale for designing new potential anticancer drugs from natural product.

To evaluate the biological preference of chiral drug candidates for molecular target DNA, the synthesis and characterization of a chiral copper(II) complex (2) of a chiral ligand N,N′-(pyridin-2-ylmethylene) dehydroabietylamine (1) was carried out. The interactions of 1 and 2 with salmon sperm DNA were investigated by viscosity measurements, UV, fluorescence and circular dichroism (CD) spectroscopic techniques. Absorption spectral, emission spectral and viscosity analysis reveal that 1 and 2 interacted with DNA through intercalation and 2 exhibited a higher DNA binding ability. In the absence/presence of ascorbic acid, 1 and 2 cleaved supercoiled pBR322 DNA by single-strand and 2 displayed stronger DNA cleavage ability. In addition, in vitro cytotoxicity of 1 and 2 against HeLa, SiHa, HepG-2 and A431 cancer cell lines study show that they exhibited effective cytotoxicity against the tested cell lines, notably, 2 showed a superior cytotoxicity than the widely used drug cisplatin under identical conditions, indicating it has the potential to act as effective anticancer drug. Flow cytometry analysis indicates 2 produced death of HeLa cancer cells through an apoptotic pathway. Cell cycle analysis demonstrates that 2 mainly arrested HeLa cells at the S phase. The study represents the first step towards understanding the mode of the promising chiral rosin-derivative based copper complexes as chemotherapeutics.

To generate potential anticancer agents, an enantiomerically pure copper(II) complex [Cu(1)Br2] (2) of a bioactive chiral ligand N,N’-(pyridin-2-ylmethylene) dehydroabietylamine (1) based on natural product rosin was synthesized. The coordination of Cu(II) has an important effect on DNA-binding, DNA cleavage and cytotoxic activity of 1. The results indicate 2 was a promising effective anticancer drug.Figure optionsDownload as PowerPoint slide