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.

Graphical abstractTo 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 full-size imageDownload as PowerPoint slide