2 research outputs found
Novel Substituted Benzothiophene and Thienothiophene Carboxanilides and Quinolones: Synthesis, Photochemical Synthesis, DNA-Binding Properties, Antitumor Evaluation and 3D-Derived QSAR Analysis
A series of new <i>N</i>,<i>N</i>-dimethylaminopropyl-
and 2-imidazolinyl-substituted derivatives of benzo[<i>b</i>]thienyl- and thieno[2,3-<i>b</i>]thienylcarboxanilides
and benzo[<i>b</i>]thieno[2,3-<i>c</i>]- and thieno[3′,2′:4,5]thieno[2,3-<i>c</i>]quinolones were prepared. Quinolones were prepared by
the reaction of photochemical dehydrohalogenation of corresponding
anilides. Carboxanilides and quinolones were tested for the antiproliferative
activity. 2-Imidazolinyl-substituted derivatives showed very prominent
activity. By use of the experimentally obtained antitumor measurements,
3D-derived QSAR analysis was performed for the set of compounds. Higly
predicitive 3D-derived QSAR models were obtained, and molecular properties
that have the highest impact on antitumor activity were identified.
Carboxanilides <b>6a</b>–<b>c</b> and quinolones <b>9a</b>–<b>c</b> and <b>11a</b> were evaluated
for DNA binding propensities and topoisomerases I and II inhibition
as part of their mechanism of action assessment. The evaluated differences
in the mode of action nicely correlate with the results of the 3D-QSAR
analysis. Taken together, the results indicate which modifications
of the compounds from the series should further improve their anticancer
properties
Metabolomics of silver nanoparticles toxicity in HaCaT cells: structure–activity relationships and role of ionic silver and oxidative stress
<p>The widespread use of silver nanoparticles (AgNPs) is accompanied by a growing concern regarding their potential risks to human health, thus calling for an increased understanding of their biological effects. The aim of this work was to systematically study the extent to which changes in cellular metabolism were dependent on the properties of AgNPs, using NMR metabolomics. Human skin keratinocytes (HaCaT cells) were exposed to citrate-coated AgNPs of 10, 30 or 60 nm diameter and to 30 nm AgNPs coated either with citrate (CIT), polyethylene glycol (PEG) or bovine serum albumin (BSA), to assess the influence of NP size and surface chemistry. Overall, CIT-coated 60 nm and PEG-coated 30 nm AgNPs had the least impact on cell viability and metabolism. The role of ionic silver and reactive oxygen species (ROS)-mediated effects was also studied, in comparison to CIT-coated 30 nm particles. At concentrations causing an equivalent decrease in cell viability, Ag<sup>+ </sup>ions produced a change in the metabolic profile that was remarkably similar to that seen for AgNPs, the main difference being the lesser impact on the Krebs cycle and energy metabolism. Finally, this study newly reported that while down-regulated glycolysis and disruption of energy production were common to AgNPs and H<sub>2</sub>O<sub>2</sub>, the impact on some metabolic pathways (GSH synthesis, glutaminolysis and the Krebs cycle) was independent of ROS-mediated mechanisms. In conclusion, this study shows the ability of NMR metabolomics to define subtle biochemical changes induced by AgNPs and demonstrates the potential of this approach for rapid, untargeted screening of pre-clinical toxicity of nanomaterials in general.</p