Palladium(II) complexes with N-heteroaromatic bidentate hydrazone ligands: The effect of the chelate ring size and lipophilicity on in vitro cytotoxic activity

Abstract

Novel Pd(II) complex with N-heteroaromatic Schiff base ligand, derived from 8-quinolinecarboxaldehyde (q8a) and ethyl hydrazinoacetate (haOEt), was synthesized and characterized by analytical and spectroscopy methods. The structure of novel complex, as well as structures of its quinoline and pyridine analogues, was optimized by density functional theory calculations, and theoretical data show good agreement with experimental results. A cytotoxic action of the complexes was evaluated on cultures of human promyelocytic leukemia (HL-60), human glioma (U251), rat glioma (C6), and mouse fibrosarcoma (L929) cell lines. Among investigated compounds, only complexes with quinoline-based ligands reduce the cell numbers in a dose-dependent manner in investigated cell lines. The observed cytotoxic effect of two isomeric quinoline-based complexes is predominantly mediated through the induction of apoptotic cell death in HL-60 cell line. The cytotoxicity of most efficient novel Pd(II) complex is comparable to the activity of cisplatin, in all cell lines investigated. The effect of the chelate ring size and complex lipophilicity on in vitro cytotoxic activity of Pd(II) complexes with NN bidentate N-heteroaromatic hydrazones was investigated. It was shown that more lipophilic complexes with quinoline backbone were more potent in the cytotoxic action than pyridine analogues. The cytotoxicity of most efficient novel Pd(II) complex 1 is comparable to the activity of cisplatin in all cell lines investigated and is predominantly mediated through the induction of apoptotic cell death. © 2014 John Wiley & Sons A/S.