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

Fiche publication

Date publication

juin 2019

Journal

Journal of inorganic biochemistry

Auteurs

Membres identifiés du Cancéropôle Est :
Dr MULLER Christian

Tous les auteurs :
Bjelogrlić SK, Todorović TR, Kojić M, Senćanski M, Nikolić M, Višnjevac A, Araškov J, Miljković M, Muller CD, Filipović NR

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/31299379

Résumé

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.