A5068147290- Metabolomics and Mass Spectrometry Studies
- Analytical Chemistry and Chromatography
- Urinary Bladder and Prostate Research
- Computational Drug Discovery Methods
- Cardiac Ischemia and Reperfusion
- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- Phytoestrogen effects and research
- Pharmacogenetics and Drug Metabolism
- Pulmonary Hypertension Research and Treatments
- Natural Compound Pharmacology Studies
- Receptor Mechanisms and Signaling
- Biotin and Related Studies
- Fatty Acid Research and Health
- Muscle metabolism and nutrition
- Click Chemistry and Applications
- Sleep and Wakefulness Research
- Neurotransmitter Receptor Influence on Behavior
- Chemical Reaction Mechanisms
- Organic Chemistry Cycloaddition Reactions
- Pelvic floor disorders treatments
- Diet and metabolism studies
- Parkinson's Disease Mechanisms and Treatments
- Cholinesterase and Neurodegenerative Diseases
- Anesthesia and Neurotoxicity Research
University of Perugia
2014-2017
Ospedale San Carlo
2012
University of Siena
2007-2009
Hetero-bifunctional PROteolysis TArgeting Chimeras (PROTACs) represent a new emerging class of small molecules designed to induce polyubiquitylation and proteasomal-dependent degradation target protein. Despite the increasing number publications about synthesis, biological evaluation, mechanism action PROTACs, characterization pharmacokinetic properties this compounds is still minimal. Here, we report study on metabolism series 40 PROTACs in cryopreserved human hepatocytes at multiple time...
To date, the main limitations for LC-MS-based untargeted lipidomics reside in lack of adequate computational and cheminformatics tools that are able to support analysis several thousands species from biological samples, enabling data mining automating lipid identification external prediction processes. address these issues, we developed Lipostar, novel vendor-neutral high-throughput software effectively supports both targeted LC-MS lipidomics, implementing acquisition, user-friendly...
Significance The metabolism of xenobiotics is a critical aspect drug discovery; nowadays, aldehyde oxidase (AOX) has emerged as key metabolic enzyme having pivotal role in the failures several clinical candidates. lack homogenous data on possible substrates and not this represents serious limit for development an silico model prediction. Here, we present database 270 chemically diverse compounds containing aza-aromatic and/or amide moieties (susceptible to human AOX), experimentally tested...
FMO enzymes (FMOs) play a key role in the processes of detoxification and/or bioactivation specific pharmaceuticals and xenobiotics bearing nucleophilic centers. The N-oxide S-oxide metabolites produced by FMOs are often active metabolites. more than cytochromes brain work tandem with CYP3A4 liver. might reduce risk phospholipidosis CAD-like drugs, although some seem to be neurotoxic hepatotoxic. However, silico methods for metabolism prediction not yet available. This paper reports, first...
The regulation of brain monoamine levels is paramount for cognitive functions, and the oxidase (MAO A B) enzymes play a central role in these processes. aim this study was to evaluate whether procognitive properties exerted by propargylamine N-(furan-2-ylmethyl)-N-methylprop-2-yn-1-amine (F2MPA) are related changes content via MAO inhibition. In vivo microdialysis ex amine metabolite measurement demonstrated region-specific alterations metabolism that differ from both classic B inhibitors,...
Cytochrome P450 (CYP) isozymes vary their expression depending on the brain area, cell type, and presence of drugs. Some isoforms are involved in detoxification and/or toxic activation xenobiotics central nervous system. However, role metabolism neurodegeneration is still a subject debate. We have studied inducibility CYP human neuroblastoma SH-SY5Y cells, treated with β-naphtoflavone (β-NF) or ethanol (EtOH) as inducers, by qRT-PCR, Western blot (WB), metabolic activity assays....
The aim of this study was to investigate the effect 17beta-oestradiol (E(2)) on detrusor smooth muscle contractility and its possible neuroprotective role against ischaemic-like condition, which could arise during overactive bladder disease. E(2) investigated rat strips stimulated with carbachol, KCl electrically, in absence or presence a selective oestrogen receptor antagonist (ICI 182,780) and, by using confocal Ca(2+) imaging technique, measuring amplitude (DeltaF/F(0)) frequency...
The importance of adsorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis is expected to grow substantially due recent failures in detecting severe issues new chemical entities during preclinical/clinical development. Traditionally, safety risk assessment studies for humans have been conducted animals advanced preclinical or clinical phase drug However, potential now needs be detected the discovery process as soon possible without reliance on animal studies. "omics",...
The field of targeted protein degradation, through the control ubiquitin–proteasome system (UPS), is progressing considerably; to exploit this new therapeutic modality, proteolysis targeting chimera (PROTAC) technology was born. opportunity use PROTACs engaging E3 ligases that can hijack and UPS could greatly extend applicability degrading molecules. To end, here we show a potential application ELIOT (E3 LIgase pocketOme navigaTor) platform, previously published by group, for...
To investigate the effects of anoxia and glucopenia (A-G) on both male female guinea pig urinary bladder.In whole bladders superfused with oxygenated Krebs' solution, intrinsic nerves underwent electrical field stimulation (EFS) smooth muscle stimulated carbachol, ATP, high potassium. The effect 1, 2, or 3 hr A-G contractile response ensuing recovery in was monitored. Glycogen content also measured.Under different stimuli bladder proved to contract more efficiently than organ. After 1 EFS...
Abstract Aim To study the effect of 17β‐estradiol (E 2 ) as a neuroprotective agent in male and female rat urinary bladders subjected to Anoxia‐Glucopenia Reperfusion (A/G‐R) damage. Methods Rat were exposed 1 hour A—G hours reperfusion (R). Intrinsic nerves underwent electrical field stimulation. The E on contractile response its recovery R phase, was monitored by adding it bath medium, at different concentrations, 60 min before A—G, during first 30 R. Furthermore, both genders, vivo...
To investigate the effect of St John's wort (SJW) and its active constituents hypericin hyperforin on detrusor smooth muscle contractility their possible neuroprotective role against ischaemic-like conditions, which could arise during overactive bladder disease.In whole bladders, intrinsic nerves underwent electrical field stimulation (EFS). The drugs contractile response recovery in reperfusion phase (R) was monitored at different concentrations 1 or 2 h anoxia-glucopenia (A-G) first 30 min...