Search results for "A549"
showing 10 items of 67 documents
Caged Dexamethasone/Quercetin Nanoparticles, Formed of the Morphogenetic Active Inorganic Polyphosphate, are Strong Inducers of MUC5AC
2021
Inorganic polyphosphate (polyP) is a widely distributed polymer found from bacteria to animals, including marine species. This polymer exhibits morphogenetic as well as antiviral activity and releases metabolic energy after enzymatic hydrolysis also in human cells. In the pathogenesis of the coronavirus disease 2019 (COVID-19), the platelets are at the frontline of this syndrome. Platelets release a set of molecules, among them polyP. In addition, the production of airway mucus, the first line of body defense, is impaired in those patients. Therefore, in this study, amorphous nanoparticles of the magnesium salt of polyP (Mg-polyP-NP), matching the size of the coronavirus SARS-CoV-2, were pr…
Steroidal glycosides from Ornithogalum dubium Houtt
2018
The phytochemical study of Ornithogalum dubium Houtt. (Asparagaceae) led to the isolation of five undescribed steroidal glycosides together with two known ones. Their structures were established by using NMR analysis and mass spectrometry as (25R)-3β-hydroxyspirost-5-en-1β-yl O-α-L-arabinopyranosyl-(1 → 2)-α-L-rhamnopyranoside, (25S)-3β-hydroxyspirost-5-en-1β-yl O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside, (22S)-16β-[(α-L-rhamnopyranosyl)oxy]-22-hydroxycholest-5-en-3β-yl O-β-D-glucopyranosyl-(1 → 4)-β-D-glucopyranoside, (22S,23S)-1β,3β,11α,16β,23-pentahydroxy-5α-cholest-24-en-22β-yl β-D-glucopyranoside, (22S,23S)-3β-[(β-D-glucopyranosyl)oxy]-22,23-dihydroxy-5α-cholest-24-en-16β-yl O-α-…
Identification of 2-(thiophen-2-yl)acetic Acid-Based Lead Compound for mPGES-1 Inhibition.
2021
We report the implementation of our in silico/synthesis pipeline by targeting the glutathione-dependent enzyme mPGES-1, a valuable macromolecular target in both cancer therapy and inflammation therapy. Specifically, by using a virtual fragment screening approach of aromatic bromides, straightforwardly modifiable by the Suzuki-Miyaura reaction, we identified 3-phenylpropanoic acid and 2-(thiophen-2-yl)acetic acid to be suitable chemical platforms to develop tighter mPGES-1 inhibitors. Among these, compounds 1c and 2c showed selective inhibitory activity against mPGES-1 in the low micromolar range in accordance with molecular modeling calculations. Moreover, 1c and 2c exhibited interesting IC…
Comparison of the combined action of oxaliplatin or cisplatin and radiation in cervical and lung cancer cells
2007
To test the combined effects of oxaliplatin and radiation versus cisplatin and radiation using human cervical and lung cancer cell lines.CaSki cervical cancer cells, and A549 lung cancer cells were cultured under standard conditions. Cells were treated with escalating doses of gamma-irradiation (0-6 Gy), and with oxali- and cisplatin for 2 h or 24 h, or a combination of both. Cell survival was measured by a colony-forming assay. Survival curves were fitted to the data using the linear quadratic model. Sensitizer enhancement ratios (SER) were calculated at the 37% survival level, and isobologram analysis was applied to test for the drug-radiation interactions.Oxaliplatin as well as cisplatin…
Euphosantianane A–D: Antiproliferative Premyrsinane Diterpenoids from the Endemic Egyptian Plant Euphorbia Sanctae-Catharinae
2018
Euphorbia species are rich in diterpenes. A solvent extraction of Euphorbia sanctae-catharinae, a species indigenous to the Southern Sinai of Egypt, afforded several premyrsinane diterpenoids (1&ndash
Proline-Based Allosteric Inhibitors of Zika and Dengue Virus NS2B/NS3 Proteases
2019
The NS2B/NS3 serine proteases of the Zika and Dengue flaviviruses are attractive targets for the development of antiviral drugs. We report the synthesis and evaluation of a new, proline-based compound class that displays allosteric inhibition of both proteases. The structural features relevant for protease binding and inhibition were determined to establish them as new lead compounds for flaviviral inhibitors. Based on our structure-activity relationship studies, the molecules were further optimized, leading to inhibitors with submicromolar IC50 values and improved lipophilic ligand efficiency. The allosteric binding site in the proteases was probed using mutagenesis and covalent modificati…
Piclamilast inhibits the pro-apoptotic and anti-proliferative responses of A549 cells exposed to H(2)O(2) via mechanisms involving AP-1 activation.
2012
Reactive oxygen species (ROS) are involved in the pathogenesis of many inflammatory diseases such as chronic obstructive pulmonary disease (COPD). They can alter the expression of genes involved in cellular damage by activating transcription factors, including the NF-κB and the activator protein 1 (AP-1). Phosphodiesterase type 4 (PDE4) inhibitors have anti-inflammatory and antioxidant effects, as described in in vivo and in vitro COPD models. This study analysed the effects of piclamilast, a selective PDE4 inhibitor, on modulating the global gene expression profile in A549 cells exposed to H(2)O(2).Changes in gene expression were analysed using high-density Affymetrix microarrays and valid…
Modulation of endotoxin-induced neutrophil transendothelial migration by alveolar epithelium in a defined bilayer model.
2006
Within the alveolus, epithelial cells, due to their close association with endothelial cells, can potentially influence endothelial cell responsiveness during inflammation and their interaction with leukocytes. To investigate this, three lung epithelial cell lines (A549, Calu-3, or NCI-H441) were grown with endothelium on opposing surfaces of Transwell filters and the formation and stability of bilayers was rigorously evaluated. All epithelial lines disrupted endothelial monolayer formation on filters with 3- or 5-microm pores by breaching the filter, and this occurred regardless of seeding density, matrix composition, or duration of culture. Endothelial disruption was not detectable by ele…
Metabolism and bioactivation of toxicants in the lung. The in vitro cellular approach.
2005
Lung is a target organ for the toxicity of inhalated compounds. The respiratory tract is frequently exposed to elevated concentrations of these compounds and become the primary target site for toxicity. Occupational, accidental or prolonged exposure to a great variety of chemicals may result in acute or delayed injury to cells of the respiratory tract. Nevertheless, lung has a significant capability of biotransforming such compounds with the aim of reducing its potential toxicity. In some instances, the biotransformation of a given compound can result in the generation of more reactive, and frequently more toxic, metabolites. Indeed, lung tissue is known to activate pro-carcinogens (i.e. po…
Glycine-functionalized copper(ii) hydroxide nanoparticles with high intrinsic superoxide dismutase activity
2017
Superoxide dismutases (SOD) are a group of enzymes that catalyze the dismutation of superoxide (O2−) radicals into molecular oxygen (O2) and H2O2 as a first line of defense against oxidative stress. Here, we show that glycine-functionalized copper(II) hydroxide nanoparticles (Gly-Cu(OH)2 NPs) are functional SOD mimics, whereas bulk Cu(OH)2 is insoluble in water and catalytically inactive. In contrast, Gly-Cu(OH)2 NPs form water-dispersible mesocrystals with a SOD-like activity that is larger than that of their natural CuZn enzyme counterpart. Based on this finding, we devised an application where Gly-Cu(OH)2 NPs were incorporated into cigarette filters. Cigarette smoke contains high concent…