engleski

Pd(II) complexes with N-heteroaromatic hydrazone ligands: Anticancer activity, in silico and experimental target identification

Anticancer activity of Pd complexes 1–5 with bidentate N-heteroaromatic hydrazone ligands was investigated on human acute monocytic leukemia (THP-1 ; cells in a suspension) and human mammary adenocarcinoma (MCF-7 ; two-dimensional layer and three-dimensional spheroid tumor model) cell lines. For the Pd(II) complexes with condensation products of ethyl hydrazainoacetate and quinoline-8-carboxaldehyde (complex 1) and 2-formylpyridine (complex 3), for which apoptosis was determined as a mechanism of anticancer activity, further investigation revealed that they arrest the cell cycle in G0/G1 phase, induce generation of reactive oxygen species and inhibit Topoisomerase I in vitro. In silico studies corroborate experimental findings that these complexes show topoisomerase inhibition activity in the micromolar range and indicate binding to a DNA's minor groove as another potential target. Based on the results obtained by circular dichroism and fluorescence spectroscopy measurements, the most active complexes are suitable to be delivered to a blood stream via human serum albumin.

Hydrazones ; Apoptosis ; Topoisomerase inhibition ; DNAinteractions ; HSAinteractions

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