A5049965061- Computational Drug Discovery Methods
- Analytical Chemistry and Chromatography
- Metabolomics and Mass Spectrometry Studies
- Spectroscopy and Chemometric Analyses
- Pharmacogenetics and Drug Metabolism
- Protein Structure and Dynamics
- Drug Transport and Resistance Mechanisms
- Enzyme Structure and Function
- Chemical Synthesis and Analysis
- Free Radicals and Antioxidants
- Monoclonal and Polyclonal Antibodies Research
- Antioxidant Activity and Oxidative Stress
- Antibiotics Pharmacokinetics and Efficacy
- Microbial Metabolic Engineering and Bioproduction
- Biochemical and Molecular Research
- Synthesis and biological activity
- Synthesis and Biological Evaluation
- Antibiotic Resistance in Bacteria
- Cancer therapeutics and mechanisms
- Receptor Mechanisms and Signaling
- Click Chemistry and Applications
- Peptidase Inhibition and Analysis
- Colorectal Cancer Treatments and Studies
- Phenothiazines and Benzothiazines Synthesis and Activities
- Advanced Proteomics Techniques and Applications
University of Perugia
2015-2024
University of Bologna
1998-2020
Universidad de Granada
2020
University of Florida
2019
Roche (Switzerland)
2019
Mario Negri Institute for Pharmacological Research
2019
Molecular Discovery (United Kingdom)
2004-2018
University of Padua
2012
Siena Biotech (Italy)
2010
Pfizer (United Kingdom)
2007-2009
Traditional methods for performing 3D-QSAR rely upon an alignment step that is often time-consuming and can introduce user bias, the resultant model being dependent sensitive to used. There are several which overcome this problem, but in general necessary transformations prevent a simple interpretation of models original descriptor space (i.e. 3D molecular coordinates). Here we present novel class descriptors have termed GRid-INdependent Descriptors (GRIND). They derived such way as be...
Identification of metabolic biotransformations can significantly affect the drug discovery process. Since bioavailability, activity, toxicity, distribution, and final elimination all depend on biotransformations, it would be extremely advantageous if this information could produced early in phase. Once obtained, help chemists to judge whether a potential candidate should eliminated from pipeline or modified improve chemical stability safety new compounds. The use silico methods predict site...
Predicting blood-brain barrier (BBB) permeation remains a challenge in drug design. Since it is impossible to determine experimentally the BBB partitioning of large numbers preclinical candidates, alternative evaluation methods based on computerized models are desirable. The present study was conducted demonstrate value descriptors derived from 3D molecular fields estimating set compounds and produce simple mathematical model suitable for external prediction. method used (VolSurf) transforms...
A fast new algorithm (Fingerprints for Ligands And Proteins or FLAP) able to describe small molecules and protein structures using a common reference framework of four-point pharmacophore fingerprints molecular-cavity shape is described in detail. The procedure starts by the GRID force field calculate molecular interaction fields, which are then used identify particular target locations where an energetic with features would be very favorable. points thus calculated FLAP build all possible...
One of the most important physicochemical properties a molecule is pKa. It known that two parameters imperative in ADME profiling, solubility, and lipophilicity are governed by pKa, receptor binding can be influenced Because drugs ionized physiological conditions, pKa particularly relevant to medicinal chemistry. Despite numerous advances high-throughput measurements, silico determination still fastest cheapest way obtaining This paper presents new original computational method for...
Abstract An advanced variable selection procedure, called GOLPE, aimed at obtaining PLS regression models with the highest prediction ability is presented and illustrated an application in 3D‐QSAR. Key steps procedure are a preliminary by means of D‐optimal design loading space, iterative evaluation effects individual variables on model predictivity based validation number reduced models, combinations selected according to FFD strategy. The successfully applied real 3D‐QSAR case study:...
A large number of substituted chalcones have been synthesized and tested for antileishmanial lymphocyte-suppressing activities. subset the was designed by using statistical methods. 3D-QSAR analyses 67 (antileishmanial activity) 63 (lymphocyte-suppressing compounds training sets 9 as an external validation set were performed GRID/GOLPE methodology. The Smart Region Definition procedure with subsequent region selection implemented in GOLPE reduced variables to approximately 1300 yielding...
Through the years GRID force field has been tuned to fit experimental observations in crystal structures. This paper describes determination of hydrogen bonding pattern for organic fluorines based on an exhaustive inspection Protein Data Bank. All PDB complexes, whose protein structures have cocrystallized fluorine-containing ligands, were examined and geometrically inspected. By applying statistics, geometry was described as a distribution function angle at fluorine: new specific angular...
Abstract Given the three‐dimensional structure of a protein, how can one find sites where other molecules might bind to it? Do these have properties necessary for high affinity binding? Is this protein suitable target drug design? Here, we discuss recent developments in computational methods address and related questions. Geometric identify pockets on surfaces been developed over many years but, with new algorithms, their performance is still improving. Simulation show promise accounting...
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...
Tautomeric rearrangements affect the results of cheminformatics applications that depend on knowledge 2D or 3D structure a compound, such as tools for database searches, fingerprint generation, virtual screening, and physical-chemical properties prediction. In this paper we present TauThor, tool to enumerate tautomers predict tautomer stability in aqueous medium. The enumeration is based recursive process generates according general scheme HX-Y=Z left harpoon over right X=Y-ZH. calculated by...
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...
The aim of this study was to establish the persistence severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on inanimate surfaces such as plastic, stainless steel, and glass during UV-C irradiation which is a physical means commonly utilized in sanitization procedures. viral inactivation rate, virus half-life, percentage titer reduction after were assessed. Infectivity maintained plastic until 120 h steel 72 h. half-life 5.3, 4.4, 4.2 glass, respectively. In all cases, decay >99%...
Mass Spectrometry Imaging (MSI) is an established and powerful MS technique that enables molecular mapping of tissues cells finding widespread applications in academic, medical, pharmaceutical industries. As both the MSI technology have undergone rapid growth improvement, challenges associated with analyzing large datasets identifying many detected species become apparent. The lack readily available comprehensive software covering all necessary data analysis steps has further compounded this...
Abstract Although second-line antiandrogen therapy (SAT) is the standard of care in men with castration-resistant prostate cancer (CRPC), resistance inevitably occurs. One major proposed mechanism to SAT involves emergence androgen receptor (AR) splice variant-7, AR-V7. Recently, we developed MTX-23 using principle proteolysis targeting chimera (PROTAC) target both AR-V7 and AR-full length (AR-FL). has been designed simultaneously bind AR's DNA binding domain (DBD) Von Hippel–Lindau (VHL) E3...
Viral infections sustain their replication cycle promoting a pro-oxidant environment in the host cell. In this context, specific alterations of levels and homeostatic function tripeptide glutathione have been reported to play causal role cytopathic effects (CPE) virus. study, these aspects were investigated for first time SARS-CoV2-infected Vero E6 cells, reliable well-characterized vitro model infection. SARS-CoV2 markedly decreased cellular thiols, essentially lowering reduced form (GSH)....