A5011230969- Neuroscience and Neuropharmacology Research
- Chemical Synthesis and Analysis
- Enzyme Catalysis and Immobilization
- Click Chemistry and Applications
- Analytical Chemistry and Chromatography
- Biochemical and Molecular Research
- Synthesis and Biological Evaluation
- Amino Acid Enzymes and Metabolism
- Crystallization and Solubility Studies
- Molecular Sensors and Ion Detection
- X-ray Diffraction in Crystallography
- Trypanosoma species research and implications
- Innovative Microfluidic and Catalytic Techniques Innovation
- Synthesis of heterocyclic compounds
- Metal complexes synthesis and properties
- Synthesis and Reactions of Organic Compounds
- Pharmacological Receptor Mechanisms and Effects
- Carbohydrate Chemistry and Synthesis
- Receptor Mechanisms and Signaling
- Microbial Metabolic Engineering and Bioproduction
- Drug Transport and Resistance Mechanisms
- Asymmetric Synthesis and Catalysis
- Cancer therapeutics and mechanisms
- Estrogen and related hormone effects
- Ion channel regulation and function
University of Milan
2016-2025
University of Catania
2024-2025
University of Pavia
1999-2024
University of Siena
2024
Mylan (South Africa)
2015-2016
University of Chieti-Pescara
2014
European Institute of Oncology
2012
National Cancer Institute
2012
Kaw Nation
2011
Capella University
2011
ADVERTISEMENT RETURN TO ISSUEPREVLetterNEXTDesign of Remarkably Simple, Yet Potent Urea-Based Inhibitors Glutamate Carboxypeptidase II (NAALADase)Alan P. Kozikowski, Fajun Nan, Paola Conti, Jiazhong Zhang, Epolia Ramadan, Tomasz Bzdega, Barbara Wroblewska, Joseph H. Neale, Sergey Pshenichkin, and Jarda T. WroblewskiView Author Information Drug Discovery Program, Department Neurology, Pharmacology, Georgetown University Medical Center, 3900 Reservoir Road, N.W., Washington, D.C. 20007,...
A series of Δ(2)-isoxazoline constrained analogues procaine/procainamide (7a-k and 8a-k) were prepared their inhibitory activity against DNA methyltransferase 1 (DNMT1) was tested. Among them, derivative 7b is far more potent in vitro (IC(50) = 150 μM) than other non-nucleoside inhibitors also exhibits a strong dose-dependent antiproliferative effect HCT116 human colon carcinoma cells. The binding mode with the enzyme investigated by means simple competition assay as well docking simulations...
Rhodesain, a cathepsin L-like cysteine protease of T. brucei rhodesiense, is considered potential target for the treatment human African trypanosomiasis. Recent findings have confirmed that rhodesain, lysosomal protease, essential parasite survival. Rhodesain required by to cross blood-brain barrier, degrade host immunoglobulins, and turn over variant surface coat glycoproteins brucei, which impair effective immune responses. In this Perspective, we discuss main classes rhodesain inhibitors,...
Glutamate is the major excitatory neurotransmitter of central nervous system (CNS) and may induce cytotoxicity through persistent activation glutamate receptors oxidative stress. Its extracellular concentration maintained at physiological concentrations by high affinity transporters solute carrier 1 family (SLC1). also present in islet Langerhans where it secreted α-cells acts as a signaling molecule to modulate hormone secretion. Whether plays role cell viability presently unknown. We...
We developed a new class of covalent inhibitors Plasmodium falciparum glyceraldehyde-3-phosphate dehydrogenase, validated target for the treatment malaria, by screening small library 3-bromo-isoxazoline derivatives that inactivate enzyme through covalent, selective bond to catalytic cysteine, as demonstrated mass spectrometry. Substituents on isoxazolinic ring modulated potency up 20-fold, predominantly due an electrostatic effect, assessed computational analysis.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and devastating human malignancies. In about 70% PDACs tumor suppressor gene TP53 mutated generally resulting in conformational changes mutant p53 (mutp53) proteins, which acquire oncogenic functions triggering aggressiveness cancers alteration energetic metabolism. Here, we demonstrate that prevents nuclear translocation glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) stabilizing its cytoplasmic...
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been proposed as chemopreventive agents for many tumours; however, the mechanism responsible their anti-neoplastic activity remains elusive and side effects due to cyclooxygenase (COX) inhibition prevent this clinical application. Molecular biology, in silico, cellular vivo tools, including innovative imaging classical biochemical assays, were applied identify characterise COX-independent anti-cancer of NSAIDs. Here, we show that...
Abstract The chemoenzymatic flow synthesis of enantiomerically pure captopril, a widely used antihypertensive drug, is accomplished starting from simple, inexpensive, and readily available reagents. first step heterogeneous biocatalyzed regio‐ stereoselective oxidation cheap prochiral 2‐methyl‐1,3‐propandiol, performed in using immobilized whole cells Acetobacter aceti MIM 2000/28, thus avoiding the use aggressive environmentally harmful chemical oxidants. isolation highly hydrophilic...
NMDA-type glutamate receptors are ligand-gated ion channels that contribute to excitatory neurotransmission in the central nervous system (CNS). Most NMDA comprise two glycine-binding GluN1 and glutamate-binding GluN2 subunits (GluN2A-D). We describe highly potent (S)-5-[(R)-2-amino-2-carboxyethyl]-4,5-dihydro-1H-pyrazole-3-carboxylic acid (ACEPC) competitive antagonists, of which ST3 has a binding affinity 52 nM at GluN1/2A 782 GluN1/2B receptors. This 15-fold preference for over is...
Abstract Novel rhodesain inhibitors were obtained by combining an enantiomerically pure 3‐bromoisoxazoline warhead with a specific peptidomimetic recognition moiety. All derivatives behaved as of rhodesain, low micromolar K i values. Their activity against the enzyme was found to be paralleled in vitro antitrypanosomal activity, IC 50 values mid‐micromolar range. Notably, preference for parasitic over human proteases, specifically cathepsins B and L, observed.
A growing interest in the study of aerobic glycolysis as a key pathway for cancer-cell energetic metabolism, favouring tumour progression and invasion, has led to consider GAPDH an effective drug target specifically hit cancer cells. In this study, we have investigated panel 3-bromo-isoxazoline derivatives based on previously identified inhibitors Plasmodium falciparum (PfGAPDH). The compounds are active, different extent, human-recombinant GAPDH. They showed antiproliferative effect...
Enterococcus faecalis is responsible for numerous serious infections, and treatment options often include ampicillin combined with an aminoglycoside or dual beta-lactam therapy a third-generation cephalosporin. The mechanism of relies on the saturation penicillin-binding proteins (PBPs). Ceftobiprole exhibits high affinity binding to nearly all E. PBPs, thus suggesting its potential utility in severe infections. availability therapeutic drug monitoring (TDM) ceftobiprole has prompted use...
Natural hydroxycinnamic acid amides (HCAAs) and riparins offer significant health benefits. However, their extraction from natural sources is difficult, traditional synthetic methods remain wasteful, raising the need for more efficient alternatives. In this work, a two-step chemo-enzymatic flow method esterification amidation of phenolic acids was developed successfully applied to synthesis riparin derivatives HCAAs. The Fischer optimized using vanillic as model starting material SiliaBond...
Abstract Acivicin analogues with an increased affinity for CTP synthetase (CTPS) were designed as potential new trypanocidal agents. The inhibitory activity against CTPS can be improved by increasing molecular complexity, inserting groups able to establish additional interactions the binding pocket of enzyme. This strategy has been pursued synthesis α‐amino‐substituted and N1‐substituted pyrazoline derivatives. In general, there is direct correlation between enzymatic in vitro...