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Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents
Published on: May 28, 2014
Anticancer Behavior of Pyrrolidine-Based Palladium(II) Complexes and Biophysical Approach on Their DNA, BSA Binding
Swarup Kumar Tarai1, Angana Pan1, Pritam Biswas2
1Department of Chemistry, National Institute of Technology Durgapur, Durgapur, West Bengal 713209, India.
Abstract:
A series of pyrrolidine-based Pd(II) complexes, [Pd(AEP)Cl2] (C-1), [Pd(AEP)(OH2)2]2+(C-2), [Pd(AEP)(L-cys)]+ (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-(2-aminoethyl)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.
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