Pd(II) complexes with N-heteroaromatic hydrazone ligands: Anticancer activity, in silico and experimental target identification
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AuthorsBjelogrlić, Snežana K.
Kojić, Milan O.
Muller, Christian D.
Filipović, Nenad R.
Article (Published version)
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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 ac...tive complexes are suitable to be delivered to a blood stream via human serum albumin.
Keywords:Apoptosis / DNA interactions / HSA interactions / Hydrazones / Pd(II) complexes / Topoisomerase I inhibition
Source:Journal of Inorganic Biochemistry, 2019, 199
- Interactions of natural products, their derivatives and coordination compounds with proteins and nucleic acids (RS-172055)
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3319