A5012413508- Computational Drug Discovery Methods
- Animal testing and alternatives
- Effects and risks of endocrine disrupting chemicals
- Cholinesterase and Neurodegenerative Diseases
- Pesticide Residue Analysis and Safety
- Metabolomics and Mass Spectrometry Studies
- Pharmacogenetics and Drug Metabolism
- Remote-Sensing Image Classification
- Spectroscopy and Chemometric Analyses
- Geochemistry and Geologic Mapping
- Carcinogens and Genotoxicity Assessment
- Analytical Chemistry and Chromatography
- Chemistry and Chemical Engineering
- Environmental Toxicology and Ecotoxicology
- Drug-Induced Hepatotoxicity and Protection
- Scientific Computing and Data Management
- Drug Transport and Resistance Mechanisms
- Genetics, Bioinformatics, and Biomedical Research
- Health Systems, Economic Evaluations, Quality of Life
- Receptor Mechanisms and Signaling
- Agricultural safety and regulations
- Redox biology and oxidative stress
- Pharmaceutical and Antibiotic Environmental Impacts
- Pesticide Exposure and Toxicity
- Research on scale insects
Mario Negri Institute for Pharmacological Research
2016-2025
Istituti di Ricovero e Cura a Carattere Scientifico
2015-2025
University of Bari Aldo Moro
2013-2017
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...
The median lethal dose for rodent oral acute toxicity (LD50) is a standard piece of information required to categorize chemicals in terms the potential hazard posed human health after exposure. exclusive use vivo testing limited by time and costs performing experiments need sacrifice number animals. (Quantitative) structure-activity relationships [(Q)SAR] proved valid alternative reduce assist assays assessing toxicological hazard. In framework new international collaborative project, NTP...
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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The quality of data used for QSAR model derivation is extremely important as it strongly affects the final robustness and predictive power model. Ambiguous or wrong structures need to be carefully checked, because they lead errors in calculation descriptors, hence leading meaningless results. increasing amounts data, however, have often made hard check very large databases manually. In light this, we designed implemented a semi-automated workflow integrating structural retrieval from several...
Nonalcoholic hepatic steatosis is a worldwide epidemiological concern since it among the most prominent diseases. Indeed, research in toxicology and epidemiology has gathered evidence that exposure to endocrine disruptors can perturb cellular homeostasis cause this disease. Therefore, assessing likelihood of chemical trigger matter utmost importance. However, systematic vivo testing all chemicals humans are exposed not feasible for ethical economical reasons. In context, predicting molecular...
Physiologically based kinetic (PBK) modelling offers a mechanistic basis for predicting the pharmaco-/toxicokinetics of compounds and thereby provides critical information integrating toxicity exposure data to replace animal testing with in vitro or silico methods. However, traditional PBK depends on human data, which limits its usefulness non-animal To address this limitation, high-throughput aims rely exclusively model generation. Here, we evaluate variety tools different strategies...
Drug-induced liver injury (DILI) is a major cause of drug development failures and postmarket withdrawals, posing significant challenges to public health pharmaceutical research. The biological mechanisms leading DILI are highly complex the adverse reaction often difficult foresee. Hence, mechanistic insights into DILI, as well machine learning models predict molecular events that trigger outcomes, pharmacokinetics pharmacodynamics in liver, essential tools for understanding preventing DILI....
The REACH (Registration, Evaluation, Authorization and restriction of Chemicals) BPR (Biocide Product Regulation) regulations strongly promote the use non-animal testing techniques to evaluate chemical risk. This has renewed interest towards alternative methods such as QSAR in regulatory context. assessment Bioconcentration Factor (BCF) required by these is expensive, terms costs, time, laboratory animal sacrifices. Herein, we present models based on ANTARES dataset, which a large collection...
The potential for a compound to cause hepatotoxicity and nephrotoxicity is matter of extreme interest human health risk assessment. To assess liver kidney toxicity, repeated-dose toxicity (RDT) studies are conducted mainly on rodents. However, these tests expensive, time-consuming require large numbers animals. For early screening, in silico models can be applied, reducing the costs, time animals used. Among approaches, structure–activity relationship (SAR) methods, based identification...
Read-across approaches often remain inconclusive as they do not provide sufficient evidence on a common mode of action across the category members. This read-across case study thirteen, structurally similar, branched aliphatic carboxylic acids investigates concept using human-based new approach methods, such in vitro and silico models, to demonstrate biological similarity. Five out thirteen analogues have preclinical vivo studies. Three them induced lipid accumulation or hypertrophy studies...
Drug-induced cardiotoxicity is a common side effect of drugs in clinical use or under postmarket surveillance and commonly due to off-target interactions with the cardiac human-ether-a-go-go-related (hERG) potassium channel. Therefore, prioritizing drug candidates based on their hERG blocking potential mandatory step early preclinical stage discovery program. Herein, we trained properly validated 30 ligand-based classifiers hERG-related 7,963 curated compounds extracted by freely accessible...
Developmental and adult/ageing neurotoxicity is an area needing alternative methods for chemical risk assessment. The formulation of a strategy to screen large numbers chemicals highly relevant due potential exposure compounds that may have long-term adverse health consequences on the nervous system, leading neurodegeneration. Adverse Outcome Pathways (AOPs) provide information molecular initiating events (MIEs) key (KEs) could inform development computational alternatives these complex...