A5047719830- Cannabis and Cannabinoid Research
- Axon Guidance and Neuronal Signaling
- Mast cells and histamine
- Receptor Mechanisms and Signaling
- Circadian rhythm and melatonin
- Alcohol Consumption and Health Effects
- Neurotransmitter Receptor Influence on Behavior
- Cancer therapeutics and mechanisms
- Free Radicals and Antioxidants
- Lung Cancer Treatments and Mutations
- HER2/EGFR in Cancer Research
- Olfactory and Sensory Function Studies
- Synthesis and biological activity
- Pharmacological Receptor Mechanisms and Effects
- Chromatography in Natural Products
- Gut microbiota and health
- Computational Drug Discovery Methods
- Tryptophan and brain disorders
- Adenosine and Purinergic Signaling
- Polyamine Metabolism and Applications
- Biochemical effects in animals
- Angiogenesis and VEGF in Cancer
- Neuroscience and Neuropharmacology Research
- Chemical Synthesis and Reactions
- GABA and Rice Research
University of Parma
2016-2025
Istituto di Farmacologia Traslazionale
2015
University Hospitals Parma Medical Center
2015
Italian Institute of Technology
2008
University of Urbino
2008
University of Milan
2003
Here, we report on a mechanistic investigation based DFT calculations and kinetic measures aimed at determining the energetics related to cysteine nucleophilic attack nitrile-carrying compounds. Activation energies were found correlate well with experimental of reactivity in phosphate buffer. The agreement between computations experiments points this DFT-based approach as tool for predicting both nitrile toward cysteines toxicity nitriles electrophile agents.
Tuberculosis remains one of the deadliest infectious diseases in world, and increased number multidrug-resistant extremely drug-resistant strains is a significant reason for concern. This makes discovery novel antitubercular agents cogent priority. We have previously addressed this need by reporting series substituted 2-aminothiazoles capable to inhibit growth actively replicating, nonreplicating persistent, resistant Mycobacterium tuberculosis strains. Clues from structure–activity...
The fatty acid ethanolamides are a class of signaling lipids that include agonists at cannabinoid and alpha type peroxisome proliferator-activated receptors (PPARalpha). In the brain, these compounds primarily hydrolyzed by intracellular serine enzyme amide hydrolase (FAAH). O-aryl carbamate FAAH inhibitors such as URB597 being evaluated clinically for treatment pain anxiety, but interactions with carboxylesterases in liver might limit their usefulness. Here we explore two strategies aimed...
Malaria eradication is a global health priority, but current therapies are not always suitable for providing radical cure. Artemisinin has paved the way malaria treatment, so-called Artemisinin-based Combination Therapy (ACT). However, with detection of resistance to ACT, innovative compounds active against multiple parasite species and at life stages needed. GlaxoSmithKline recently disclosed results phenotypic screening an internal library, publishing collection 400 antimalarial...
ABSTRACT Since cheese is one of the most commonly and globally consumed fermented foods, scientific investigations in recent decades have focused on determining impact this dairy product human health well-being. However, modulatory effect exerted by autochthonous microbial community taxonomic composition associated functional potential gut microbiota still far from being fully dissected or understood. Here, through use an vitro gut-simulating cultivation model combination with multi-omics...
Alkylcarbamic acid biphenyl-3-yl esters are a class of fatty amide hydrolase (FAAH) inhibitors that comprises cyclohexylcarbamic 3′-carbamoylbiphenyl-3-yl ester (URB597), compound with analgesic, anxiolytic-like and antidepressant-like properties in rat mouse models. Here, we extended the structure−activity relationships (SARs) for this compounds by replacing cyclohexyl ring parent (URB524) (FAAH IC50 = 63 nM) selected set substituents different size, shape, flexibility, lipophilicity....
Exposure of C2C12 muscle cells to hypertonic stress induced an increase in cell content creatine transporter mRNA and transport activity, which peaked after about 24 h incubation at 0.45 osmol (kg H 2 O) −1 . This induction activity was prevented by addition either cycloheximide, inhibit protein synthesis, or actinomycin D, RNA synthesis. Creatine uptake these is largely Na + dependent kinetic analysis revealed that its under conditions resulted from V max the ‐dependent component, with no...
Irreversible epidermal growth factor receptor (EGFR) inhibitors contain a reactive warhead which covalently interacts with conserved cysteine residue in the kinase domain. The acrylamide fragment, commonly employed warhead, effectively alkylates Cys797 of EGFR, but its reactivity can cause rapid metabolic deactivation or nonspecific reactions off-targets. We describe here new series irreversible containing 3-aminopropanamide linked position 6 to 4-anilinoquinazoline...
The fatty acid ethanolamides (FAEs) are a family of bioactive lipid mediators that include the endogenous agonist peroxisome proliferator-activated receptor-α, palmitoylethanolamide (PEA). FAEs hydrolyzed intracellularly by either amide hydrolase or N-acylethanolamine-hydrolyzing amidase (NAAA). Selective inhibition NAAA (S)-N-(2-oxo-3-oxetanyl)-3-phenylpropionamide [(S)-OOPP, 7a] prevents PEA degradation in mouse leukocytes and attenuates responses to proinflammatory stimuli. Starting from...
The β-lactone ring of N-(2-oxo-3-oxetanyl)amides, a class N-acylethanolamine acid amidase (NAAA) inhibitors endowed with anti-inflammatory properties, is responsible for both NAAA inhibition and low compound stability. Here, we investigate the structure-activity structure-property relationships set known new derivatives, focusing on N-(2-oxo-3-oxetanyl)carbamates. Replacement amide group carbamate one led to different stereoselectivity higher intrinsic stability, because reduced level...
A green protocol for SPPS allows the recovery and recycling of solvents bases from process waste mixture.
Irreversible EGFR inhibitors can circumvent acquired resistance to first-generation reversible, ATP-competitive in the treatment of non-small-cell lung cancer. They contain both a driver group, which assures target recognition, and warhead, generally an acrylamide or propargylamide fragment that binds covalently Cys797 within kinase domain EGFR. We performed systematic exploration role for warhead introducing different cysteine-trapping fragments at position 6 traditional...
4-Quinolone-3-carboxamide derivatives have long been recognized as potent and selective cannabinoid type-2 receptor (CB2R) ligands. With the aim to improve their physicochemical properties, basically aqueous solubility, two different approaches were followed, entailing substitution of alkyl chain with a basic replacement or scaffold modification 4-hydroxy-2-quinolone structure. According first approach, compound 6d was obtained, showing slightly reduced affinity (K(i) = 60 nM) compared lead...
On the basis of a previously discovered anti-αVβ3 integrin peptidomimetic (c(AmpRGD)) and clinically approved antiangiogenic kinase inhibitor sunitinib, three novel dual conjugates were synthesized (compounds 1-3), featuring covalent robust linkage between these two active modules. In all conjugates, ligand binding competence toward αVβ3 (using both isolated receptors αVβ3-overexpressing endothelial progenitor EP cells) inhibitory activity (toward kinases EPCs) remained almost untouched...
Metadynamics (META-D) is emerging as a powerful method for the computation of multidimensional free-energy surface (FES) describing protein-ligand binding process. Herein, FES unbinding antagonist N-(3α-hydroxy-5β-cholan-24-oyl)-l-β-homotryptophan (UniPR129) from its EphA2 receptor was reconstructed by META-D simulations. The characterization minima identified on this proposes mode fully consistent with previously reported and new structure-activity relationship data. To validate mode,...
The identification of a green, versatile, user-friendly, and efficient methodology is necessary to facilitate the use Heck-Cassar-Sonogashira (HCS) cross-coupling reaction in drug discovery industrial production pharmaceutical segment. Heck-Cassar Sonogashira protocols, using N-hydroxyethylpyrrolidone (HEP)/water/N,N,N',N'-tetramethyl guanidine (TMG) as green solvent/base mixture sulfonated phosphine ligands, allowed recycle catalyst, always guaranteeing high yields fast conversion under...
Pharmacological inhibition of fatty acid amide hydrolase (FAAH) activity has antidepressant-like effects in preclinical models stress. In this study, we investigated whether the FAAH are associated with corresponding changes gut microbial and lipidomic profiles, which emerging as critical components pathophysiology depression. Adult male Wistar rats experienced five weeks repeated social defeat or control procedure were treated inhibitor URB694 (0.3 mg/kg/day, i.p.) vehicle starting from...
Osimertinib, a tyrosine kinase inhibitor targeting mutant EGFR, has received approval for initial treatment in patients with Non-Small Cell Lung Cancer (NSCLC). While effective both first- and second-line treatments, eventually develop acquired resistance. Metabolic reprogramming represents strategy through which cancer cells may resist adapt to the selective pressure exerted by drug. In current study, we investigated metabolic adaptations associated osimertinib-resistance NSCLC under low...