A novel platinum(ii) complex with a berberine derivative as a potential antitumor agent targeting G-quadruplex DNA

Abstract

G-quadruplexes are considered attractive targets for various human diseases, including cancer therapy, owing to their potential therapeutic applications. Understanding the interaction between ligands and G-quadruplexes is crucial for the development of novel anticancer agents. In this study, we designed a novel platinum(II) complex (Pt1), with a berberine derivative (L) serving as a bioactive ligand. The structures of both ligand L and Pt1 were fully characterized using NMR, ESI-MS, and IR. UV-visible spectroscopy, fluorescence spectroscopy, circular dichroism spectroscopy, electrostatic surface potential, frontier molecular orbital and molecular docking experiments were employed to investigate the interaction between Pt1 and G-quadruplexes. The results suggested that Pt1 interacted favorably with G-quadruplex DNA over double-stranded DNA (DS26). Among them, Pt1 interacts with the bcl-2 G-quadruplex with a binding affinity of 17.9 μM and did not induce conformational changes in the topology of the bcl-2 G-quadruplex. Moreover, we evaluated its antiproliferative activities on tumor cells (HeLa, A549 and T24), which demonstrated that Pt1 inhibited tumor cell proliferation and induced HeLa cell apoptosis. Overall, this study offers novel insights for the development of promising platinum(II) antitumor agents based on G-quadruplex structures.