Three Pt-Pt Complexes with Donor-acceptor Feature: Anticancer Activity, DNA Binding Studies and Molecular Docking Simulation

Abstract

Background: Due to their unique properties and potential applications in variety of areas, recently, a special attention is given to the binuclear platinum (II) complexes. They reveal a highly tunable features upon the modification of their cyclometallating and bridging ligands.

Objective: The aim of this study was to evaluate the anticancer activity and DNA binding affinity of three binuclear platinum (II) complexes, including ht-[(p-FC₆H₄)Pt(µ-PN)(µ-NP)PtMe₂](CF₃CO₂)(1), ht-[(p- MeC₆H₄)Pt(µ-PN)(μ-NP)Pt(p MeC₆H₄) Me] (CF₃CO₂)(2) and ht-[Pt₂Me₃(µ-PN)2](CF₃CO₂) (3).

Methods: MTT assay was performed to study the cell viability of Jurkat and MCF-7 lines against synthesized complexes, followed by apoptosis detection experiments. Several spectroscopic methods with molecular docking simulation were also used to investigate the detail of interaction of these platinum complexes with DNA.

Results: Cell viability assay demonstrated a notable level of cytotoxicity for the synthetic platinum complexes. Further studies proved that a pathway of cell signaling initiating the apoptosis might be activated by these complexes, particularly in the case of complexes 1 and 2. The results of both UV-visible and CD measurements showed the significant ability of these complexes to interact with DNA. While fluorescence data revealed that these complexes cannot enter DNA structure by intercalation, molecular docking assessment proved their DNA groove binding ability.

Conclusion: The remarkable apoptosis inducing activity of the binuclear platinum complexes 1 and 2 and their considerable interaction with DNA suggest them as the potential antitumor medicines.

Keywords: Binuclear platinum (II) complexes; apoptosis; electrophoresis; flow cytometry; molecular docking; spectroscopic study..