Anticancer Behavior of Pyrrolidine-Based Palladium(II) Complexes and Biophysical Approach on Their DNA, BSA Binding Activity, Molecular Docking, and DFT Study

Abstract

A series of pyrrolidine-based Pd(II) complexes, [Pd(AEP)Cl 2 ] (C-1), [Pd(AEP)(OH 2 ) 2 ] 2+ (C-2), [Pd(AEP)(Lcys)] + (C-3), [Pd(AEP)(N-ac-L-cys)] (C-4), [Pd(AEP)(GSH)] (C-5), and [Pd(AEP)(DL-meth)] 2+ (C-6) (where, AEP = 1-(2aminoethyl)pyrrolidine, L-cys = L-cysteine, N-ac-L-cys = N-acetyl-L-cysteine, GSH = glutathione, and DL-meth = DL-methionine), as anticancer drug candidates have been synthesized and characterized. The DNA binding property of the complexes was executed by gel electrophoresis and spectrophotometric and viscometric methods, and their interaction with BSA was also investigated by various spectroscopic methodologies. The binding activity of the Pd(II) complexes with DNA and BSA were assessed to evaluate their binding mode and binding constants. Molecular docking was performed to correlate with the experimental results on the interaction of the complexes with DNA and BSA. The changes in the microenvironmental and structural properties of BSA are monitored by a synchronous and 3D fluorescence study. The structural properties were evaluated by DFT and TD-DFT studies. The anticarcinogenic activity of the Pd(II) complexes was assessed by PASS prediction software to corroborate with the experimental results of the anticancer activity of the complexes. The ROS generation in cancer cell lines has been investigated, and the cell death mechanism through apoptosis was confirmed by measuring the protein expression. All these complexes have excellent anticancer activity compared to ancillary ligands. The cancer cell line (HCT116) shows almost similar or better cell inhibition activity when treated with the Pd(II) complexes compared to cisplatin, whereas the adverse effect is minimum on a normal cell (NKE). Both the Pd(II) and Pt(II) complexes carrying the same ligands reveal almost similar antiproliferative activity.

Modulating the aggregation of human prion protein PrP106–126 by an indole-based cyclometallated palladium complex

“…Palladium complexes have been the subject of much research as potential anticancer drugs because of their ability to bind to DNA. 68–70 Such complexes interact with polypeptide fragments, proteins, and enzymes. Considering these studies, we have calculated the DNA binding of the complex through UV-visible spectroscopy ( K b = 8.9 × 10 5 M −1 ) and fluorescence spectroscopy ( K SV = 3.9 × 10 4 M −1 ) (ESI Fig.…”