A5024737795- Computational Drug Discovery Methods
- Cholinesterase and Neurodegenerative Diseases
- Synthesis and biological activity
- Chemical Synthesis and Analysis
- Electrochemical sensors and biosensors
- Chemistry and Chemical Engineering
- Synthesis and Biological Evaluation
- Click Chemistry and Applications
- Pharmacogenetics and Drug Metabolism
- Ion channel regulation and function
- Microbial Natural Products and Biosynthesis
- Chemical synthesis and alkaloids
- Analytical Chemistry and Chromatography
- Cardiac electrophysiology and arrhythmias
- Estrogen and related hormone effects
- Peptidase Inhibition and Analysis
- Machine Learning in Materials Science
- Protease and Inhibitor Mechanisms
- Effects and risks of endocrine disrupting chemicals
- Metabolomics and Mass Spectrometry Studies
- Animal testing and alternatives
- Receptor Mechanisms and Signaling
- Nicotinic Acetylcholine Receptors Study
- Alzheimer's disease research and treatments
- Protein Structure and Dynamics
University of Bari Aldo Moro
2016-2025
Istituto di Farmacologia Traslazionale
2025
University of Cagliari
2021
Universidade de Santiago de Compostela
2006
University of Sheffield
2000-2002
Background:Humans are exposed to thousands of man-made chemicals in the environment. Some mimic natural endocrine hormones and, thus, have potential be disruptors. Most these never been tested for their ability interact with estrogen receptor (ER). Risk assessors need tools prioritize evaluation costly vivo tests, instance, within U.S. EPA Endocrine Disruptor Screening Program.Objectives:We describe a large-scale modeling project called CERAPP (Collaborative Estrogen Receptor Activity...
Quantitative Structure-Activity Relationships are widely acknowledged predictive methods employed, for years, in organic and medicinal chemistry. More recently, they have assumed a central role also the context of explorative toxicology protection environment human health. However, their real-life application has not been always enthusiastically welcomed, being often retrospectively used and, thus, limited importance prospective goals. The need making more trustable predictions thus...
Background: Endocrine disrupting chemicals (EDCs) are xenobiotics that mimic the interaction of natural hormones and alter synthesis, transport, or metabolic pathways. The prospect EDCs causing adverse health effects in humans wildlife has led to development scientific regulatory approaches for evaluating bioactivity. This need is being addressed using high-throughput screening (HTS) vitro computational modeling. Objectives: In support Disruptor Screening Program, U.S. Environmental...
Generative models have revolutionized de novo drug design, allowing to produce molecules on-demand with desired physicochemical and pharmacological properties. String based molecular representations, such as SMILES (Simplified Molecular Input Line Entry System) SELFIES (Self-Referencing Embedded Strings), played a pivotal role in the success of generative approaches, thanks their capacity encode atom- bond- information ease-of-generation. However, 'atom-level' string representations could...
The multifactorial nature of Alzheimer's disease calls for the development multitarget agents addressing key pathogenic processes. To this end, by following a docking-assisted hybridization strategy, number aminocoumarins were designed, prepared, and tested as monoamine oxidases (MAOs) acetyl- butyryl-cholinesterase (AChE BChE) inhibitors. Highly flexible N-benzyl-N-alkyloxy coumarins 2-12 showed good inhibitory activities at MAO-B, AChE, BChE but low selectivity. More rigid inhibitors,...
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Aiming at modulating two key enzymatic targets for Alzheimer's disease (AD), i.e., acetylcholinesterase (AChE) and monoamine oxidase B (MAO B), a series of multitarget ligands was properly designed by linking the 3,4-dimethylcoumarin scaffold to 1,3- 1,4-substituted piperidine moieties, thus basicity improve hydrophilic/lipophilic balance. After in vitro inhibition assays, multipotent inhibitors showing potencies nanomolar low micromolar range hMAO eeAChE, respectively, were prioritized...
Artificial intelligence and multiobjective optimization represent promising solutions to bridge chemical biological landscapes by addressing the automated de novo design of compounds as a result humanlike creative process. In present study, we conceived novel pair-based approach implemented in an adapted SMILES generative algorithm based on recurrent neural networks for new molecules whose overall features are optimized finding best trade-offs among relevant physicochemical properties (MW,...
PLATO (Polypharmacology pLATform predictiOn) is an easy-to-use drug discovery web platform, which has been designed with a two-fold objective: to fish putative protein targets and compute bioactivity values of small molecules. Predictions are based on the similarity principle, through reverse ligand-based screening, collection 632,119 compounds known be experimentally active 6004 targets. An efficient backend implementation allows speed-up process that returns results for query in less than...
Despite being extremely relevant for the protection of prenatal and neonatal health, developmental toxicity (Dev Tox) is a highly complex endpoint whose molecular rationale still largely unknown. The lack availability high-quality data as well robust nontesting methods makes its understanding even more difficult. Thus, application new explainable alternative utmost importance, with Dev Tox one most animal-intensive research themes regulatory toxicology. Descending from TIRESIA (Toxicology...
Due to the putative role of butyrylcholinesterase (BChE) in regulation acetylcholine levels and functions late stages Alzheimer's disease (AD), potential selective inhibitors (BChEIs) has been envisaged as an alternative administration acetylcholinesterase (AChEIs). Starting from our recent findings, herein synthesis vitro evaluation cholinesterase (ChE) inhibition a novel series some twenty 3,4,5,6-tetrahydroazepino[4,3-b]indol-1(2H)-one derivatives, bearing at indole nitrogen diverse...
Abstract Molecular docking is by far the most preferred approach in structure‐based drug design for its effectiveness to predict scoring and posing of a given bioactive small molecule into binding site pharmacological target. Herein, we present MzDOCK , new GUI‐based pipeline Windows operating system, designed with intent making molecular easier use higher reproducible even inexperienced people. By harmonic integration python batch scripts, which employs various open source packages such as...
Chemical space networks (CSNs) are a new effective strategy for detecting latent chemical patterns irrespective of defined coordinate systems based on molecular descriptors and fingerprints. CSNs can be powerful option as approach method increase the capacity assessing potential adverse impacts chemicals human health. Here, shown to effectively characterize toxicity toward several health end points, namely chromosomal aberrations, mutagenicity, carcinogenicity, developmental toxicity, skin...
Background/Objectives: People affected by COVID-19 are exposed to abnormal clotting and endothelial dysfunction, which may trigger thromboembolic events. This study aimed at retrospectively investigating whether oral anticoagulant therapy (OAT), encompassing either direct anticoagulants (DOACs), mainly apixaban, or the vitamin K antagonist (VKA) warfarin, could have impacted medium-term mortality in a cohort of SARS-CoV-2 patients. Methods: Among 1238 patients, hospitalized from 17 March...
In an effort to discover novel selective monoamine oxidase (MAO) B inhibitors with favorable physicochemical and pharmacokinetic profiles, 7-[(m-halogeno)benzyloxy]coumarins bearing properly selected polar substituents at position 4 were designed, synthesized, evaluated as MAO inhibitors. Several compounds MAO-B inhibitory activity in the nanomolar range excellent selectivity (selectivity index SI > 400) identified. Structure−affinity relationships docking simulations provided valuable...
Methods that provide a measure of chemical similarity are strongly relevant in several fields chemoinformatics as they allow to predict the molecular behavior and fate structurally close compounds. One common application measurements, based on principle similar molecules have properties, is read-across approach, where an estimation specific endpoint for provided using experimental data available from highly compounds.This paper reports comparison multiple combinations binary fingerprints...
The design, synthesis, and biological evaluation of a series new aromatase (AR, CYP19) inhibitors bearing an imidazole ring linked to 7-substituted coumarin scaffold at position 4 (or 3) are reported. Many compounds exhibited inhibitory potency in the nanomolar range along with high selectivity over 17-α-hydroxylase/C17−20 lyase (CYP17). most potent AR inhibitor was 7-(3,4-difluorophenoxy)-4-imidazolylmethyl 24 endowed IC50 = 47 nM. Docking simulations on selected number derivatives allowed...
We present MuSSeL, a multifingerprint similarity search algorithm, able to predict putative drug targets for given query small molecule as well return quantitative assessment of its bioactivity in terms Ki or IC50 values. Predictions are automatically made exploiting large collection high quality experimental data available from ChEMBL (version 22.1) combining, consensus-like approach, predictions resulting performed using 13 different fingerprint definitions. Importantly, the herein...
Abstract Paramyxoviridae , a large family of enveloped viruses harboring nonsegmented negative-sense RNA genome, include important human pathogens as measles, mumps, respiratory syncytial virus (RSV), parainfluenza viruses, and henipaviruses, which cause some the deadliest emerging zoonoses. There is no effective antiviral chemotherapy for most these pathogens. Paramyxoviruses evolved sophisticated membrane-fusion machine consisting receptor-binding proteins fusion F-protein, critical...