Effects of copper ions on DNA binding and cytotoxic activity of a chiral salicylidene Schiff base

• The first chiral copper(II) binuclear complex of dehydroabityl Schiff base was synthesized.
• The copper(II) complex shows stronger binding affinity to DNA compared with the ligand.
• Our studies suggest that the binding mode between the complexes and DNA is intercalation.
• The in vitro cytotoxicity of the compounds reflects their DNA binding strength order.
• Our work provides a rationale for designing new potential anticancer drugs from natural product.

A chiral Schiff base HL N-(5-bromo-salicylaldehyde)dehydroabietylamine (1) and its chiral dinuclear copper complex [Cu2L4]·4DMF (2) have been synthesized and fully characterized. The interactions of 1 and 2 with salmon sperm DNA have been investigated by viscosity measurements, UV, fluorescence and circular dichroism (CD) spectroscopic techniques. Absorption spectral (Kb = 3.30 × 105 M−1 (1), 6.63 × 105 M−1(2)), emission spectral (Ksv = 7.58 × 103 M−1 (1), 1.52 × 104 M−1 (2)), and viscosity measurements reveal that 1 and 2 interact with DNA through intercalation and 2 exhibits a higher DNA binding ability. In addition, CD study indicates 2 cause a more evident perturbation on the base stacking and helicity of B-DNA upon binding to it. In fluorimetric studies, the enthalpy (ΔH > 0) and entropy (ΔS > 0) changes of the reactions between the compounds with DNA demonstrate hydrophobic interactions. 1 and 2 were also screened for their cytotoxic ability and 2 demonstrates higher growth inhibition of the selected cancer cells at concentration of 50 μM, this result is identical with their DNA binding ability order. All the experimental results show that the involvement of Cu (II) centers has some interesting effect on DNA binding ability and cytotoxicity of the chiral Schiff base.

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