A5103275316- Cannabis and Cannabinoid Research
- Neurotransmitter Receptor Influence on Behavior
- Toxic Organic Pollutants Impact
- Pharmacological Receptor Mechanisms and Effects
- Crystallization and Solubility Studies
- Pancreatic function and diabetes
- Analytical Chemistry and Chromatography
- X-ray Diffraction in Crystallography
- Nanocomposite Films for Food Packaging
- GABA and Rice Research
- Forensic Toxicology and Drug Analysis
- Synthesis and biological activity
- Carbohydrate Chemistry and Synthesis
- Advanced Drug Delivery Systems
- Polyamine Metabolism and Applications
- Click Chemistry and Applications
- Synthesis and Biological Evaluation
- Diet, Metabolism, and Disease
- Microbial bioremediation and biosurfactants
- Research on Leishmaniasis Studies
- Neuroscience and Neuropharmacology Research
- Drug Transport and Resistance Mechanisms
- Antimicrobial agents and applications
- Receptor Mechanisms and Signaling
- Crystallography and molecular interactions
University of Eastern Finland
2010-2023
Medical University of Lublin
2016
Finland University
2013
University of Iceland
2004-2005
London School of Hygiene & Tropical Medicine
2003
Radboud University Nijmegen
2002
Finnvera (Finland)
2000
University of Jyväskylä
1991-1996
The blood−brain barrier efficiently controls the entry of drug molecules into brain. We describe a feasible means to achieve carrier-mediated transport rat brain via specific, large neutral amino acid transporter (LAT1) by conjugating model compound l-tyrosine. A hydrophilic drug, ketoprofen, that is not substrate for LAT1 was chosen as compound. mechanism and kinetics uptake prodrug were determined with an in situ perfusion technique. found be concentration-dependent. In addition, specific...
An efficient five-step synthetic route was developed for full N-substitution of chitosan with a quaternary betaine moiety. The procedure can also be controlled to produce N-betainates having lesser degrees substitution. 6-O-Triphenylmethylchitosan, which is highly soluble in organic solvents, used as an intermediate N-acylation reactions. Intermediate products were characterized by 13C CP/MAS NMR, FT-IR, and elemental analysis. water-soluble thoroughly 1H NMR 2D 1H−1H COSY 13H−1H HSQC NMR....
In the present study, identification of chiral 1,3,4-oxadiazol-2-ones as potent and selective FAAH inhibitors has been described. The separated enantiomers showed clear differences in potency selectivity toward both MAGL. Additionally, importance chirality on inhibitory activity was proven by simplification approach removing a methyl group at 3-position 1,3,4-oxadiazol-2-one ring. most compound series, S-enantiomer 3-(1-(4-isobutylphenyl)ethyl)-5-methoxy-1,3,4-oxadiazol-2(3H)-one (JZP-327A,...
Water-soluble phosphate prodrugs of buparvaquone (1), containing a hydroxynaphthoquinone structure, were synthesized and evaluated in vitro for improved topical oral drug delivery against cutaneous visceral leishmaniasis. The successfull prodrug synthesis involved strong base; e.g., sodium hydride. Buparvaquone-3-phosphate (4a) 3-phosphonooxymethyl-buparvaquone (4b) possessed significantly higher aqueous solubilities (>3.5 mg/mL) than the parent (≤0.03 μg/mL) over pH range 3.0−7.4. Moreover,...
A series of commercial phenyl-, heteroaryl-, alkyl-, and alkenylboronic acids were evaluated for their FAAH MGL inhibitory activities. The compounds generally selective FAAH, with IC50 in the nanomolar or low-micromolar range. Eight these inhibited micromolar most potent compound, phenylboronic acid para-nonyl substituent (13), 0.0091 7.9 microM, respectively.
Background Human lymphocyte antigen B-associated transcript 5 (BAT5, also known as ABHD16A) is a poorly characterized 63 kDa protein belonging to the α/β-hydrolase domain (ABHD) containing family of metabolic serine hydrolases. Its natural substrates and biochemical properties are unknown. Methodology/Principal Findings Amino acid sequence comparison between seven mammalian BAT5 orthologs revealed that overall primary structure was highly (≥95%) conserved. Activity-based profiling (ABPP)...
Fatty acid amide hydrolase (FAAH) is an intracellular serine hydrolase, which catalyzes the hydrolysis of endocannabinoid N-arachidonoylethanolamide to arachidonic and ethanolamine. FAAH also hydrolyzes another endocannabinoid, 2-arachidonoylglycerol (2-AG). However, 2-AG has been assumed be hydrolyzed mainly by monoacylglycerol lipase (MAGL) or a MAGL-like enzyme. Inhibition MAGL activity might lead beneficial effects in many physiological disorders such as pain, inflammation, anxiety due...
Various hormone-sensitive lipase (HSL) inhibitors, such as oxadiazolones, 2H-isoxazol-5-ones and carbamoyltriazoles, were evaluated for their fatty acid amide hydrolase (FAAH) monoglyceride (MGL) inhibitory potencies. All compounds inhibited both enzymes with IC50 values varying from the nanomolar to low micromolar range. The may serve lead structures in development of novel potentially selective FAAH MGL inhibitors. Detailed facts importance specialist readers are published "Supporting...
The human constitutive androstane receptor (CAR, NR1I3) is one of the key regulators xenobiotic and endobiotic metabolism. unique properties CAR, such as high activity complexity signaling, well lack functional predictive cell-based assays to study receptor, have hindered discovery selective CAR ligands. Here we report a novel inverse agonist, 1-[(2-methylbenzofuran-3-yl)methyl]-3-(thiophen-2-ylmethyl) urea (S07662), which suppresses activity, recruits corepressor NCoR in assays, attenuates...
The primary route of inactivation the endocannabinoid 2-arachidonoylglycerol in central nervous system is through enzymatic hydrolysis, mainly carried out by monoacylglycerol lipase (MAGL), along with a small contribution <i>α</i>/<i>β</i>-hydrolase domain (ABHD) proteins ABHD6 and ABHD12. Recent methodological progress allowing kinetic monitoring glycerol liberation has facilitated substrate profiling human hydrolases, these studies have revealed that three enzymes distinct isomer...
The highly CB2 selective cannabinoid receptor inverse agonist, 7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid N-benzo[1,3]dioxol-5-ylmethyl)amide (JTE-907; 9b), served as the lead compound for investigating structure−activity relationships of its analogues and in search more potent effective agonists. A series aromatic amides 6 was synthesized, activities compounds were determined by a [35S]GTPγS-binding assay using membranes CHO cells stably transfected with human...
To identify novel selective CB2 lead compounds, a comparative model of the receptor was constructed using high-resolution bovine rhodopsin X-ray structure as template. The utilized both in building database queries and filtering hit compounds by docking scoring method. In G-protein activation assays, 1-isoquinolyl[3-(trifluoromethyl)phenyl]methanone (40, NRB 04079) found to act agonist at human receptor.
The endocannabinoid system remains an attractive molecular target for pharmacological intervention due to its roles in the central nervous learning, thinking, emotional function, regulation of food intake or pain sensation, as well peripheral system, where it modulates action cardiovascular, immune, metabolic reproductive function. α/β hydrolase domain containing 6 (ABHD6)—an enzyme forming part system—is a newly discovered post-genomic protein acting 2-AG (2-arachidonoylglycerol) serine...