Search results for " DISCOVERY"
showing 10 items of 4082 documents
A Comprehensive Spectroscopic Analysis of the Ibuprofen Binding with Human Serum Albumin, Part I
2020
Human serum albumin (HSA) plays a fundamental role in the human body. It takes part in the transport of exogenic and endogenic substances, especially drugs. Ibuprofen (IBU) is one of the most commonly used non-steroidal anti-inflammatory drugs, used for pain relief, fever relief, and for anti-inflammatory purposes. The binding of ligands with HSA is a significant factor which determines the toxicity and the therapeutic dosages of these substances. The aim of this study was to compare the degree of ibuprofen binding with human serum albumin at various temperatures and protein solution pH values. In order to evaluate conformational changes in HSA caused by interaction with ibuprofen, spectrop…
Identification of potential therapeutic compounds for Parkinson's disease using Drosophila and human cell models.
2017
Abstract Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. It is caused by a loss of dopaminergic neurons in the substantia nigra pars compacta, leading to a decrease in dopamine levels in the striatum and thus producing movement impairment. Major physiological causes of neurodegeneration in PD are oxidative stress (OS) and mitochondrial dysfunction; these pathophysiological changes can be caused by both genetic and environmental factors. Although most PD cases are sporadic, it has been shown that 5–10% of them are familial forms caused by mutations in certain genes. One of these genes is the DJ-1 oncogene, which is involved in an early…
Drug Distribution to Retinal Pigment Epithelium: Studies on Melanin Binding, Cellular Kinetics, and Single Photon Emission Computed Tomography/Comput…
2016
Melanin binding is known to affect the distribution and elimination of ocular drugs. The purpose of this study was to evaluate if the extent of drug uptake to primary retinal pigment epithelial (RPE) cells could be estimated based on in vitro binding studies with isolated melanin and evaluate the suitability of single photon emission computed tomography/computed tomography (SPECT/CT) in studying pigment binding in vivo with pigmented and albino rats. Binding of five compounds, basic molecules timolol, chloroquine, and nadolol and acidic molecules methotrexate and 5(6)-carboxy-2',7'-dichlorofluorescein (CDCF), was studied using isolated melanin from porcine choroid-RPE at pH 5.0 and 7.4. The…
PPAR Agonists, Atherogenic Dyslipidemia and Cardiovascular Risk.
2016
Peroxisome proliferator-activated receptors (PPAR) are implicated in the pathology of several metabolic diseases including obesity, diabetes, and atherosclerosis. PPAR agonists exert multiple lipid modifying actions which are beneficial to the prevention of atherosclerosis. Such benefits in lipid lowering actions include improvements in atherogenic dyslipidemia that seems to be particularly expressed in individuals at higher cardiovascular (CV) risk. In addition, the favorable effects of PPAR agonists on different cardio-metabolic parameters are established in several metabolic conditions, such as diabetes mellitus, insulin resistance, and heightened systemic inflammation. The goal of this …
Pharmacogenomics of Scopoletin in Tumor Cells
2016
Drug resistance and the severe side effects of chemotherapy necessitate the development of novel anticancer drugs. Natural products are a valuable source for drug development. Scopoletin is a coumarin compound, which can be found in several Artemisia species and other plant genera. Microarray-based RNA expression profiling of the NCI cell line panel showed that cellular response of scopoletin did not correlate to the expression of ATP-binding cassette (ABC) transporters as classical drug resistance mechanisms (ABCB1, ABCB5, ABCC1, ABCG2). This was also true for the expression of the oncogene EGFR and the mutational status of the tumor suppressor gene, TP53. However, mutations in the RAS onc…
Cytotoxicity and mode of action of a naturally occurring naphthoquinone, 2-acetyl-7-methoxynaphtho[2,3-b]furan-4,9-quinone towards multi-factorial dr…
2017
Abstract Introduction Malignacies are still a major public concern worldwide and despite the intensive search of new chemotherapeutic agents, treatment still remains a challenging issue. The present study was designed to evaluate the cytotoxicity of 2-acetyl-7-methoxynaphtho[2,3-b]furan-4,9-quinone (AMNQ) isolated from the bark of Milletia versicolor towards a panel of drug-sensitive and multidrug-resistant (MDR) cancer cell lines. Methods The resazurin reduction assay was used to evaluate the cytotoxicity of AMNQ against 9 drug-sensitive and multidrug-resistant (MDR) cancer cell lines. Cell cycle, mitochondrial membrane potential (MMP) and levels of reactive oxygen species were all analyze…
Treatment of Multidrug-Resistant Leukemia Cells by Novel Artemisinin-, Egonol-, and Thymoquinone-Derived Hybrid Compounds
2018
Two major obstacles for successful cancer treatment are the toxicity of cytostatics and the development of drug resistance in cancer cells during chemotherapy. Acquired or intrinsic drug resistance is responsible for almost 90% of treatment failure. For this reason, there is an urgent need for new anticancer drugs with improved efficacy against cancer cells, and with less toxicity on normal cells. There are impressive examples demonstrating the success of natural plant compounds to fight cancer, such as Vinca alkaloids, taxanes, and anthracyclines. Artesunic acid (ARTA), a drug for malaria treatment, also exerts cytotoxic activity towards cancer cells. Multidrug resistance often results fro…
Estrogen Receptor Signaling and the PI3K/Akt Pathway Are Involved in Betulinic Acid-Induced eNOS Activation
2016
Betulinic acid (BA) is a naturally occurring pentacyclic triterpenoid with anti-inflammatory, antiviral and anti-cancer properties. Beneficial cardiovascular effects such as increased nitric oxide (NO) production through enhancement of endothelial NO synthase (eNOS) activity and upregulation of eNOS expression have been demonstrated for this compound. In the present study, immortalized human EA.hy 926 endothelial cells were incubated for up to 1 h with 1–100 µM BA and with the phosphatidylinositol-3-kinase (PI3K) inhibitors LY294002 and wortmannin, or the estrogen receptor (ER) antagonist ICI 182,780. Phosphorylation status of eNOS and total eNOS protein were analyzed by Western blotting us…
Chemical Composition of Herbal Macerates and Corresponding Commercial Essential Oils and Their Effect on Bacteria Escherichia coli
2017
This study addresses the chemical composition of some commercial essential oils (clove, juniper, oregano, and marjoram oils), as well as appropriate herbal extracts obtained in the process of cold maceration and their biological activity against selected Escherichia coli strains: E. coli ATTC 25922, E. coli ATTC 10536, and E. coli 127 isolated from poultry waste. On the basis of the gas chromatography-mass spectrometry (GCMS) analysis, it was found that the commercial essential oils revealed considerable differences in terms of the composition and diversity of terpenes, terpenoids and sesquiterpenes as compared with the extracts obtained from plant material. The commercial clove, oregano, a…
The Effects of N-Acetylcysteine on the Rat Mesocorticolimbic Pathway: Role of mGluR5 Receptors and Interaction with Ethanol
2021
N-acetylcysteine (NAC) is a prodrug that is marketed as a mucolytic agent and used for the treatment of acetaminophen overdose. Over the last few decades, evidence has been gathered that suggests the potential use of NAC as a new pharmacotherapy for alcohol use disorder (AUD), although its mechanism of action is already being debated. In this paper, we set out to assess both the potential involvement of the glutamate metabotropic receptors (mGluR) in the possible dual effect of NAC administered at two different doses and NAC’s effect on ethanol-induced activation. To this aim, 30 or 120 mg/kg of NAC was intraperitoneally administered to rats with the presence or absence of the negative allo…