A5066819098- Cannabis and Cannabinoid Research
- Bacterial biofilms and quorum sensing
- Biochemical and Structural Characterization
- Pancreatic function and diabetes
- Pharmacological Receptor Mechanisms and Effects
- Synthesis and Biological Evaluation
- Venomous Animal Envenomation and Studies
- Antimicrobial Peptides and Activities
- Phenothiazines and Benzothiazines Synthesis and Activities
- Polyamine Metabolism and Applications
- Bone Tissue Engineering Materials
- Forensic Toxicology and Drug Analysis
- Inhalation and Respiratory Drug Delivery
- Synthesis and biological activity
- GABA and Rice Research
- Quinazolinone synthesis and applications
- Adenosine and Purinergic Signaling
- Microbial Metabolism and Applications
- Antibiotic Resistance in Bacteria
- Amino Acid Enzymes and Metabolism
- Hair Growth and Disorders
- Synthesis of Tetrazole Derivatives
- Hops Chemistry and Applications
- Medicinal Plants and Neuroprotection
- Diet, Metabolism, and Disease
University of Helsinki
2019-2023
Pharmaceutical Biotechnology (Czechia)
2013-2018
University of Eastern Finland
2011-2016
Cadila Healthcare (India)
2006-2009
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,...
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)...
A number of analogues diaryl dihydropyrazole-3-carboxamides have been synthesized. Their activities were evaluated for appetite suppression and body weight reduction in animal models. Depending on the chemical modification selected dihydropyrazole scaffold, lead compounds--the bisulfate salt (+/-)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid morpholin-4-ylamide 26 (-)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic...
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 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...
Abstract At present, inhibitors of α/β‐hydrolase domain 6 (ABHD6) are viewed as a promising approach to treat inflammation and metabolic disorders. This article describes the development 1,2,5‐thiadiazole carbamates ABHD6 inhibitors. Altogether, 34 compounds were synthesized, their inhibitory activity was tested using lysates HEK293 cells transiently expressing human (hABHD6). Among compound series, 4‐morpholino‐1,2,5‐thiadiazol‐3‐yl cyclooctyl(methyl)carbamate (JZP‐430) potently...
The emergence of multidrug-resistant bacteria along with a declining pipeline clinically useful antibiotics has led to the urgent need for development more effective antibacterial agents. Inspired by our recent report on activity etrasimod, an immunomodulating drug candidate, we prepared series etrasimod derivatives varying substituents phenyl ring, altering central tricyclic aromatic and modifying carboxyl group. From this compounds, indole derivative 24f was identified as most potent...
This work aimed to construct 3D-QSAR CoMFA and CoMSIA models for a series of 31 FAAH inhibitors, containing the 1,3,4-oxadiazol-2-one moiety. The obtained were characterized by good statistical parameters: Q2 = 0.61, R2 0.98; 0.64, 0.93. model field contributions 54.1% 45.9% steric electrostatic fields, respectively. In model, electrostatic, steric, hydrogen bond donor, acceptor properties equal 34.6%, 23.9%, 23.4%, 18.0%, These validated applying leave-one-out technique, seven-element test...
The Oxazolidinones are a promising novel chemical synthetic class of antibiotics identified in the last two decades and have been subjected to intensive discovery efforts. They possess impressive antibacterial activity against Grampositive pathogens. act through unique mechanism inhibitory bacterial protein biosynthesis. Linezolid (ZyvoxTM) has only drug oxazolidinone reach market after USFDA approval. Here we review our efforts directed antibacterials evolved structure-activity relationship...
New classes of antibiotics are urgently needed in the fight against multidrug-resistant bacteria. Drug repurposing has emerged as an alternative approach to accelerate antimicrobial research and development. In this study, we screened a library sphingosine-1-phosphate receptor (S1PR) modulators Staphylococcus aureus identified five active compounds. Among them, etrasimod (APD334), investigational drug for treatment ulcerative colitis, displayed best inhibitory activity S. when growing...
Disrupting bacterial quorum sensing (QS) signaling is a promising strategy to combat pathogenic biofilms without the development of antibiotic resistance. Here, we report that food-associated bacteria can interfere with biofilm formation Gram-negative bacterium by targeting its AHL (acyl-homoserine lactone) QS system. This was demonstrated screening metabolic end-products different lactobacilli and propionibacteria using biofilm-forming Chromobacterium violaceum as reporter our anti-QS...
Biofilm-mediated infection is a major cause of bone prosthesis failure. The lack molecules able to act in biofilms has driven research aimed at identifying new anti-biofilm agents via chemical screens. However, be accommodate large number compounds, the testing conditions these screenings end up being typically far from clinical scenario. In this study, we assess potential applicability three previously discovered compounds part implanted medical devices by them on vitro systems that more...
Nosocomial diseases represent a huge health and economic burden. A significant portion is associated with the use of medical devices, 80% these infections being caused by bacterial biofilm. The insertion foreign material usually elicits inflammation, which can result in hampered antimicrobial capacity host immunity due to effort immune cells directed degrade material. ineffective clearance perfect opportunity for bacteria attach form In this study, we analyzed antibiofilm three naturally...
We recently identified fingolimod as a potent antibiofilm compound by screening FDA-approved drugs. To study if the antibacterial activity of could be further improved and to explore in-depth structure–activity relationships, we synthesized 28 novel derivatives evaluated their efficacy against Staphylococcus aureus grown in planktonic/single cell biofilms. The most effective were tested on preformed S. biofilms Gram-negative bacteria Acinetobacter baumannii Pseudomonas aeruginosa, using...
Multimodal imaging provides rich biological information, which can be exploited to study drug activity, disease associated phenotypes, and pharmacological responses. Here we show discovery validation of a new probe targeting the endocannabinoid α/β-hydrolase domain 6 (ABHD6) enzyme by utilizing positron emission tomography (PET) matrix-assisted laser desorption/ionization (MALDI) imaging. [18F]JZP-MA-11 as first PET ligand for in vivo ABHD6 is reported specific uptake ABHD6-rich peripheral...