Abstract
Since the potential anticancer activity of auranofin was discovered, gold compounds have attracted interest with a view to developing anticancer agents that follow cytotoxic mechanisms other than cisplatin. Two benzimidazole gold(I) derivatives containing triphenylphosphine (Au(pben)(PPh3)) (1) or triethylphosphine (Au(pben)(PEt3)) (2) were prepared and characterized by standard techniques. X-ray crystal structures for 1 and 2 were solved. The cytotoxicity of 1 and 2 was tested in human neuroblastoma SH-SY5Y cells. Cells were incubated with compounds for 24 h with concentrations ranging from 10 µM to 1 nM, and the half-maximal inhibitory concentration (IC50) was determined. 1 and 2 showed an IC50 of 2.7 and 1.6 µM, respectively. In order to better understand the type of cell death induced by compounds, neuroblastoma cells were stained with Annexin-FITC and propidium iodide. The fluorescence analysis revealed that compounds were inducing apoptosis; however, pre-treatment with the caspase inhibitor Z-VAD did not reduce cell death. Analysis of compound effects on caspase-3 activity and reactive oxygen species (ROS) production in SH-SY5Y cells revealed an antiproliferative ability mediated through oxidative stress and both caspase-dependent and caspase-independent mechanisms.
Funder
Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia
Subject
Drug Discovery,Pharmaceutical Science,Molecular Medicine
Reference62 articles.
1. Medicinal chemistry of gold anticancer metallodrugs. Metallo-Drugs: Development and Action of Anticancer Agents;Casini;Met. Ions Life Sci.,2018
2. Metal Complexes for Treating Arthritis and Diabetes;Dabrowiak,2017
3. Gold compounds for rheumatoid arthritis
4. Gold Complexes in the Treatment of;Messori,2004
5. Gold compounds as therapeutic agents for human diseases
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