Spectrophotometric and physicochemical studies on the interaction of a new platinum(IV) complex containing the drug pregabalin with calf thymus DNA

Abstract

This study was designed to examine the interaction of a platinum(IV) complex containing the drug pregabalin with calf-thymus DNA (ct-DNA) under physiological conditions. The interaction between Pt(IV) complex and ct-DNA was investigated using ultraviolet-visible (UV-vis) spectroscopy, fluorescence spectroscopy, circular dichroism (CD), viscosity, molecular docking simulation and cell culture studies. Absorption spectra of Pt(IV) complex showed hypochromism. The calculated binding constant (K_b) obtained from UV-vis absorption study was 3.6 × 10⁴ M⁻¹. Furthermore, CD study demonstrated stability of the right-handed B-form of DNA in the presence of the Pt(IV) complex. In fluorimeteric studies, the binding mode of Pt(IV) complex with DNA was studied using MB as a fluorescence probe. The results showed that the complex is able to completely displace the MB intercalative binder into DNA, indicating intercalative binding. In addition, significant change on the viscosity of ct-DNA showed that the Pt(IV) complex binds to DNA by intercalative binding. Molecular docking revealed that the Pt(IV) complex not only binds to DNA by intercalative mode, but also van der Waals interactions or hydrogen bonds are the main forces in the binding process. Furthermore, the anticancer activity of Pt(IV) complex was observed with almost 100% decrease in cancer cell counts of MCF-7 breast cancer cell lines.

Graphical Abstract

Keywords:

• Pregabalin
• Platinum(IV) complex
• DNA Interaction
• Molecular docking
• Anticancer

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Financial support from Razi University Research Center is gratefully acknowledged.