A5061984838- Analytical Chemistry and Chromatography
- Metabolomics and Mass Spectrometry Studies
- Computational Drug Discovery Methods
- Surfactants and Colloidal Systems
- Influenza Virus Research Studies
- Chemical Synthesis and Reactions
- Protein Degradation and Inhibitors
- Pharmacogenetics and Drug Metabolism
- Drug Transport and Resistance Mechanisms
- Click Chemistry and Applications
- Lipid Membrane Structure and Behavior
- Ubiquitin and proteasome pathways
- DNA and Nucleic Acid Chemistry
- Advanced Proteomics Techniques and Applications
- Retinoids in leukemia and cellular processes
- RNA and protein synthesis mechanisms
- Chemical Synthesis and Analysis
- interferon and immune responses
- Peptidase Inhibition and Analysis
- Ionic liquids properties and applications
- Protein Structure and Dynamics
- Cancer therapeutics and mechanisms
- Synthesis and biological activity
- Cancer, Lipids, and Metabolism
- RNA Interference and Gene Delivery
University of Perugia
2016-2025
Mario Negri Institute for Pharmacological Research
2019
University of Geneva
2016
University of Lausanne
2016
University of Catania
2012-2013
Molecular Discovery (United Kingdom)
2009-2011
The Ohio State University
2007
University of California, Santa Barbara
2002-2006
P-glycoprotein (Pgp or ABCB1) is an ABC transporter protein involved in intestinal absorption, drug metabolism, and brain penetration, its inhibition can seriously alter a drug's bioavailability safety. In addition, inhibitors of Pgp be used to overcome multidrug resistance. Given this dual purpose, reliable silico procedures predict are great interest. A large accurate literature collection yielded more than 1200 structures; model was then constructed using various molecular interaction...
Influenza viruses are the cause of yearly epidemics and occasional pandemics that represent a significant challenge to public health. Current control strategies imperfect there is an unmet need for new antiviral therapies. Here, we report identification small molecule compounds able effectively specifically inhibit growth influenza A B in cultured cells through targeting assembly interface viral RNA-dependent RNA polymerase. Using existing crystal structure primary protein–protein between...
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...
Abstract Lipids are a structurally diverse class of biomolecules which can undergo variety chemical modifications. Among them, lipid (per)oxidation attracts most the attention due to its significance in regulation inflammation, cell proliferation and death programs. Despite their apparent regulatory significance, molecular repertoire oxidized lipids remains largely elusive as accurate annotation modifications is complicated by low abundance often unknown, biological context-dependent...
To date, Proteolysis Targeting Chimera (PROTAC) technology has been successfully applied to mediate proteasomal-induced degradation of several pharmaceutical targets mainly related oncology, immune disorders, and neurodegenerative diseases. On the other hand, its exploitation in field antiviral drug discovery is still infancy. Recently, we described two indomethacin (INM)-based PROTACs displaying broad-spectrum activity against coronaviruses. Here, report design, synthesis, characterization...
In continuing our efforts to identify small molecules able disrupt the interaction of polymerase acidic protein–basic protein 1 (PA–PB1) subunits influenza virus (Flu) RNA-dependent RNA polymerase, this paper is devoted optimization a dihydrotriazolopyrimidine derivative, previously identified through structure-based drug discovery. The structure modifications performed around bicyclic core led identification compounds endowed with both ability PA–PB1 and anti-Flu activity no cytotoxicity....
Pharmacophore elucidation approaches are routinely used in drug discovery, primarily with the aim of determining three-dimensional arrangement common features shared by ligands interacting at site interest; these can then be to investigate structure-activity relationship between and also screen for other molecules possessing relevant features. Here we present a novel approach based on GRID molecular interaction fields derivative method FLAP that has been previously described, which provides...
The structural comparison of protein binding sites is increasingly important in drug design; identifying structurally similar can be useful for techniques such as repurposing, and also a polypharmacological approach to deliberately affect multiple targets disease pathway, or explain unwanted off-target effects. Once are identified, local differences aid the design selectivity. Such an moves away from classical "one target one drug" toward wider systems biology paradigm. Here, we report...
Antibiotic resistance represents a worldwide concern, especially regarding the outbreak of methicillin-resistant Staphylococcus aureus, common cause for serious skin and soft tissues infections. A major contributor to aureus antibiotic is NorA efflux pump, which able extrude selected antibacterial drugs biocides from membrane, lowering their effective concentrations. Thus, inhibition promising challenging strategy that would allow recycling substrate antimicrobial agents. Among inhibitors,...
Acne is a multifactorial skin disorder frequently observed during adolescence with different grades of severity. Multiple factors centering on sebum secretion are implicated in acne pathogenesis. Despite the recognized role sebum, its compositional complexity and limited analytical approaches have hampered investigation alterations specifically associated acne. To examine profiles lipid distribution 61 adolescents (29 males 32 females) were enrolled this study. Seventeen subjects presented...
Abstract Two recent randomized controlled trials demonstrated improved radiographic, histological and hepatometabolic cues of non-alcoholic steatohepatitis (NASH) in pediatric patients treated with the ω-3 fatty acid docosahexaenoic (DHA) combination vitamin D (VD) or choline (CHO) E (VE), DHA-VD DHA-CHO-VE trials, respectively). In present study we verified nutritional compliance to these DHA-based multivitamin treatments; lipidomics biomarkers reported outcome on NASH indicators were also...
Lipids are structurally diverse molecules that play a pivotal role in plethora of biological processes. However, deciphering the roles specific lipids is challenging due to existence numerous isomers. This high chemical complexity lipidome one major challenges lipidomics research, as traditional liquid chromatography-mass spectrometry (LC-MS) based approaches often not powerful enough resolve these isomeric and isobaric nuances within complex samples. Thus, uniquely suited benefits provided...
Abstract Improving the ADME profile of drug candidates is a critical step in lead optimization, and because p K affects most properties such as lipophilicity, solubility, metabolism, it extremely advantageous to predict order guide design new compounds. However, accurately (<0.5 log units) predicting by empirical methods can be challenging especially for novel series, lack knowledge on determinants (steric effects, ring H‐bonding, etc. ), limited experimental data effects specific...
Influenza virus infections represent a serious concern to public health, being characterized by high morbidity and significant mortality. To date, compounds targeting the viral ion-channel M2 or neuraminidase are drugs available for treatment of influenza, but emergence drug-resistant mutants renders search novel targets their possible inhibitors major priority. Recently, we demonstrated that RNA-dependent RNA polymerase (RdRP) complex can be an optimal target protein–protein disruption...
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...