Dna-binding and antiproliferative properties of Palladium(II) complexes with tridentate ligands

Abstract

Tridentate ligands of the type N^{N^{OH }}were obtained from the reactions between salicylaldehyde derivatives (3-ethoxy, 4-diethylamino, 4-hydroxy) and primary amines (2-picolylamine or N-phenylethylenediamine), and were used to synthesize a set of five palladium complexes of the general formula Pd(N^{NO})Cl. The new complexes were characterized by NMR spectroscopy and mass spectrometry; further confirmation of the structure of Pd-Py-OEt was provided by single-crystal XRD. A DNA-binding study confirmed the importance of the ligand on the mode of binding with ct-DNA. Four complexes possess apparent binding constants in the same range, and all are higher than that of Pd-EN-NEt2. The BSA-binding proceeds via the formation of BSA-compound adducts, with higher binding constants for the ethylene-containing example due to the more flexible ligand. Molecular docking studies identified the binding site at the cleft of BSA. Anticancer properties of the palladium complexes are poorer than those of their platinum analogues, although Pd-Py-OEt and Pd-Py-NEt2 exhibit cytotoxicity similar to that of cisplatin, and significantly better cytotoxicity towards the cancer cell line over a normal cell line. Flow cytometry analysis suggests a late apoptotic cell death pathway for Pd-Py-OEt. Pd-Py-OEt; they afford different cell cycle accumulation patterns compared to Pt-Py-OEt and cisplatin, which suggests mechanistic differences in their anticancer activities.