A5070095076- Computational Drug Discovery Methods
- Synthesis and biological activity
- Inflammatory mediators and NSAID effects
- Eicosanoids and Hypertension Pharmacology
- Free Radicals and Antioxidants
- Pharmacogenetics and Drug Metabolism
- Bioactive Compounds and Antitumor Agents
- Natural product bioactivities and synthesis
- Receptor Mechanisms and Signaling
- Plant biochemistry and biosynthesis
- Estrogen and related hormone effects
- Microbial Natural Products and Biosynthesis
- Pharmacological Effects of Natural Compounds
- Phytochemistry and Bioactive Compounds
- Morinda citrifolia extract uses
- Helminth infection and control
- Sirtuins and Resveratrol in Medicine
- Phytochemicals and Antioxidant Activities
- Hormonal Regulation and Hypertension
- Retinoids in leukemia and cellular processes
- Aldose Reductase and Taurine
- Pharmacological Receptor Mechanisms and Effects
- Cholesterol and Lipid Metabolism
- Synthesis and Reactions of Organic Compounds
- Traditional and Medicinal Uses of Annonaceae
Paracelsus Medical University
2021-2025
Universität Innsbruck
2013-2023
University of Salzburg
2021
Abstract Systemic vitamin E metabolites have been proposed as signaling molecules, but their physiological role is unknown. Here we show, by library screening of potential human metabolites, that long-chain ω-carboxylates are potent allosteric inhibitors 5-lipoxygenase, a key enzyme in the biosynthesis chemoattractant and vasoactive leukotrienes. 13-((2 R )-6-hydroxy-2,5,7,8-tetramethylchroman-2-yl)-2,6,10-trimethyltridecanoic acid (α-T-13′-COOH) can be synthesized from α-tocopherol...
Geranyl flavones have been studied as compounds that potentially can be developed anti-inflammatory agents. A series of natural geranylated flavanones was isolated from Paulownia tomentosa fruits, and these were for their activity possible mechanism action. Two new characterized [paulownione C (17) tomentodiplacone O (20)], all the derivatives assayed ability to inhibit cyclooxygenases (COX-1 COX-2) 5-lipoxygenase (5-LOX). The tested showed variable degrees activity, with several them...
Pesticide levels are generally monitored within agricultural areas, but commonly not assessed at public places. To assess possible contamination of non-target 71 playgrounds located next to intensively managed apple and wine orchards were selected in four valleys South Tyrol (northern Italy). Further, the impact environmental site characteristics on number concentration pesticides was assessed. Grass samples from collected screened for 315 pesticide residues using standard gas chromatography...
Cyclooxygenases and lipoxygenases are proinflammatory enzymes; the former affects platelet aggregation, vasoconstriction, vasodilatation later development of atherosclerosis. Red wines from Georgia central western Europe inhibited cyclooxygenase-1 (COX-1) activity in range 63–94%, cyclooxygenase-2 (COX-2) 20–44% (tested at a concentration 5 mL/L), 5-lipoxygenase (5-LOX) 72–84% (at 18.87 mL/L). White 5-LOX 41–68% mL/L did not inhibit COX-1 COX-2. Piceatannol (IC 50 = 0.76 μ M) was identified...
There is an increasing interest in the development of soluble epoxide hydrolase (sEH) inhibitors, which block degradation endogenous anti-inflammatory epoxyeicosatrienoic acids. Within this study, a set pharmacophore models for sEH inhibitors was developed. The Specs database virtually screened and cell-free activity assay used biological investigation virtual hits. In total, out 48 tested compounds, 19 were with IC50 < 10 μM, representing prospective true positive hit rate 40%. Six these...
Background: Pharmacophore modeling has become an integrated tool in drug discovery. However, no prospective study compares the performance of available software. Methods: The two widely used pharmacophore and screening software programs Discovery Studio LigandScout were to generate, validate, prospectively apply COX-1 -2 models. Selected virtual hits tested cell-free enzymatic assays. correct retrieval active compounds was compared. Results: In testing, 10.5% for COX-2 6.6% predicted active....
Arachidonic acid (AA) is metabolized to diverse bioactive lipid mediators. Whereas the 5-lipoxygenase-activating protein (FLAP) facilitates AA conversion by 5-lipoxygenase (5-LOX) pro-inflammatory leukotrienes (LTs), soluble epoxide hydrolase (sEH) degrades anti-inflammatory epoxyeicosatrienoic acids (EETs). Accordingly, dual FLAP/sEH inhibition might be advantageous drugs for intervention of inflammation. We present in vivo pharmacological profile and efficiency...
Selective cyclooxygenase-1 (COX-1) inhibition has got into the spotlight with discovery of COX-1 upregulation in various cancers and cardioprotective role control thrombocyte aggregation. Yet, COX-1-selective inhibitors are poorly explored. Thus, three series quinazoline derivatives were prepared tested for their potential inhibitory activity toward COX-2. Of compounds, 11 exhibited interesting selectivity, 8 compounds being totally COX-1-selective. The IC50 value best inhibitor was 64 nM....
Abstract Leukotrienes (LTs) are pro-inflammatory lipid mediators derived from arachidonic acid (AA) with roles in inflammatory and allergic diseases. The biosynthesis of LTs is initiated by transfer AA via the 5-lipoxygenase-activating protein (FLAP) to 5-lipoxygenase (5-LO). FLAP inhibition abolishes LT formation exerting anti-inflammatory effects. soluble epoxide hydrolase (sEH) converts AA-derived epoxyeicosatrienoic acids (EETs) dihydroxyeicosatetraenoic (di-HETEs). Its consequently also...
Introduction: Lipid mediators (LM) comprise bioactive metabolites of polyunsaturated fatty acids, including pro-inflammatory prostaglandins (PG), thromboxanes (TX), and leukotrienes (LT) but also specialized pro-resolving (SPM). They are essentially biosynthesized via cyclooxygenase (COX) lipoxygenase (LO) pathways in complex networks regulate the progression resolution inflammatory disorders inflammation-triggered cancer. Ginkgolic acid (GA) is a phenolic contained Ginkgo biloba L. with...
1,4-Benzoquinones are well-known inhibitors of 5-lipoxygenase (5-LOX, the key enzyme in leukotriene biosynthesis), but molecular mechanisms 5-LOX inhibition not completely understood. Here we investigated mode action and pharmacological profile novel 1,4-benzoquinone derivative 3-((decahydronaphthalen-6-yl)methyl)-2,5-dihydroxycyclohexa-2,5-diene-1,4-dione (RF-Id) vitro its effectiveness vivo.Mechanistic investigations cell-free assays using other enzymes associated with eicosanoid...
Over the last twenty years, tocotrienol analogues raised great interest because of their higher level and larger domain biological activities when compared with tocopherols. Amongst most promising therapeutic application, anti-inflammatory potency has been evaluated through inhibition various mediators inflammation. Here, we worked on isolation two natural isoforms garcinoic acid (i.e., <i>δ</i> <i>γ</i>) from different sources, respectively, <i>Garcinia kola</i> seeds amplexicaulis</i>...
Abstract The alpine plant Cicerbita alpina (L.) Wallr., when grown as a sprout, is known bitter-tasting culinary delicacy. Recently it has also been reported to have anthelmintic activity, prompting further investigation into its mechanism of action. Liquid–liquid fractions were prepared from methanolic extract the aerial parts and submitted in parallel embryo development (ED), worm motility (WMT), cytotoxicity assays for toxicity evaluations. anthelminthic revealed more polar be most active...
Pesticides are essential in agriculture for protecting crops and boosting productivity, but their widespread use may pose significant health risks. Farmworkers face direct exposure through skin contact inhalation, which lead to hormonal imbalances, neurological disorders, elevated cancer Moreover, pesticide residues food water affect surrounding communities. One of the lesser investigated issues is immunotoxicity, mostly because chronic effects compound very complex study. As a case study,...
Pesticides are essential in agriculture for protecting crops and boosting productivity, but their widespread use may pose significant health risks. Farmworkers face direct exposure through skin contact inhalation, which lead to hormonal imbalances, neurological disorders, elevated cancer Moreover, pesticide residues food water affect surrounding communities. One of the lesser investigated issues is immunotoxicity, mostly because chronic effects compound very complex study. As a case study,...