Anticancer property and normal cell toxicity profile of pyrrolidine-based platinum (II) complexes: Their DNA, BSA interaction, and molecular docking

The bioactivity and cytotoxic property of cis-[Pt (AEP)Cl-2] (C-1); [Pt (AEP)(OH2)(2)](NO3)(2) (C-2); [Pt (AEP)(GSH) (C-3)]; and [Pt (AEP)(DL-meth)](2+)(C-4) (where AEP = 1-[2-Aminoethyl] pyrrolidine; GSH = Glutathione; DL-meth = DL-methionine) were extensively investigated to find out the more active and less toxic anticancer lead molecules. Spectroscopically characterized Pt (II) complexes (C-1 to C-4) were under investigation for their anticancer activity and bio-molecular interaction with DNA and BSA. The binding property of the complexes toward DNA and BSA were evaluated by UV-Vis, fluorescence spectroscopy, gel electrophoresis, cyclic voltammetry (CV), circular dichroism (CD), and viscometric methods for their pharmacokinetic and pharmacodynamics importance. The BSA binding activity as well as their Drug reservoir property of Pt (II) complexes were highlighted for their biological significance. Furthermore, to assess the manner of interaction and also binding strength of the complexes with DNA and BSA molecule, a theoretical approach by molecular docking was performed, utilizing the optimized structure of the complexes. Structural optimization has been performed with density functional theory (DFT) correlation functional (B3LYP) at 6-31G + (d, p) and LANL2DZ basis set was used for C, N, H, O, S, and metal, respectively. In vitro anticancer activity and level of ROS generation in presence of each complex were explored on A549 cancer cell as well as normal human cell lines HEK293, and their potential cytotoxic property was observed as compared to well-known recognized anticancer cisplatin.

Automated summary

The bioactivity and cytotoxicity of four platinum complexes were investigated to discover more active and less toxic anticancer lead molecules. The interaction of the complexes with DNA and BSA was evaluated using various methods, and their pharmacokinetic and pharmacodynamic importance was determined. Molecular docking was performed to assess the interaction mode and binding strength of the complexes with DNA and BSA. In vitro cell experiments revealed their anticancer activity and cytotoxicity.