A5051548402- Cholinesterase and Neurodegenerative Diseases
- Computational Drug Discovery Methods
- Synthesis and biological activity
- Alzheimer's disease research and treatments
- Chemical synthesis and alkaloids
- Click Chemistry and Applications
- Synthesis and Biological Evaluation
- Medicinal Plants and Neuroprotection
- X-ray Diffraction in Crystallography
- Chemical Synthesis and Analysis
- Phenothiazines and Benzothiazines Synthesis and Activities
- Crystallization and Solubility Studies
- Cancer therapeutics and mechanisms
- Pharmacogenetics and Drug Metabolism
- Multicomponent Synthesis of Heterocycles
- Drug Transport and Resistance Mechanisms
- Electrochemical sensors and biosensors
- Parkinson's Disease Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Photoreceptor and optogenetics research
- Protease and Inhibitor Mechanisms
- Peptidase Inhibition and Analysis
- Photochromic and Fluorescence Chemistry
- Receptor Mechanisms and Signaling
- Tryptophan and brain disorders
University of Bari Aldo Moro
2016-2025
University of Sassari
2015
University of Genoa
2015
University of Lausanne
2000-2007
Universidade de Santiago de Compostela
2006-2007
University of Geneva
2006
Peoples' Friendship University of Russia
2004
University of Amsterdam
1985
Western Infirmary
1977
University of Glasgow
1977
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...
A set of 17 coumarin and 2 chromone derivatives with known inhibitory activity toward monoamine oxidase (MAO) B were tested as acetylcholinesterase (AChE) inhibitors. All compounds inhibited AChE values in the micromolar range (3-100 microM). kinetic study showed that most acted noncompetitive This finding may be interest context Alzheimer's disease because recent observations suggest MAO inhibition might decrease beta-amyloid deposition.
A large series of coumarin derivatives (71 compounds) were tested for their monoamine oxidase and B (MAO-A MAO-B) inhibitory activity. Most the compounds acted preferentially on MAO-B with IC50 values in micromolar to low-nanomolar range; high activities toward MAO-A also measured sulfonic acid esters. The most active compound was 7-[(3,4-difluorobenzyl)oxy]-3,4-dimethylcoumarin, an value 1.14 nM. QSAR study 7-X-benzyloxy meta-substituted 3,4-dimethylcoumarin acting yielded good statistical...
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,...
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...
Neurodegenerative diseases such as Alzheimer's disease (AD) are multifactorial with several different pathologic mechanisms. Therefore, it is assumed that multitargeted-directed ligands (MTDLs) which interact biological targets relevant to the diseases, might offer an improved therapeutic alternative than using traditional "one-target, one-molecule" approach. Herein, we describe new benzothiazole-based derivatives a privileged scaffold for histamine H3 receptor (H3R). The most affine...
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 Amyloid aggregation is linked to a number of neurodegenerative syndromes, the most prevalent one being Alzheimer's disease. In this pathology, β‐amyloid peptides (Aβ) aggregate into oligomers, protofibrils, and fibrils eventually plaques, which constitute characteristic hallmark Several low‐molecular‐weight compounds able impair Aβ process have been recently discovered; yet, detailed description their interactions with oligomers hitherto missing. Here, molecular dynamics simulations...
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...
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...
1. A radiographic investigation of a group 241 men who had worked in compressed air at pressures up to 35 pounds per square inch gauge on the construction tunnels under River Clyde showed that forty-seven (19 cent) one or more lesions aseptic necrosis bone. 2. The radiological have been classified as juxta-articular, which may lead pain and limitation movement, head, neck shaft lesions, are usually symptomless. In 10 cent were juxta-articular therefore potentially disabling. treatment...
Bioisosteric H/F or CH2OH/CF2H replacement was introduced in coumarin derivatives previously characterized as dual AChE-MAO B inhibitors to probe the effects on both inhibitory potency and drug-likeness. Along with vitro screening, we investigated early-ADME parameters related solubility lipophilicity (Sol7.4, CHI7.4, log D7.4), oral bioavailability central nervous system (CNS) penetration (PAMPA-HDM PAMPA-blood-brain barrier (BBB) assays, Caco-2 bidirectional transport study), metabolic...
Monoamine oxidases A and B (MAO A, B) are ubiquitous enzymes responsible for oxidative deamination of amine neurotransmitters xenobiotics. Despite decades studies, MAO inhibitors (MAOIs) find today limited therapeutic space as second-line drugs the treatment depression Parkinson's disease. In recent years, a renewed interest in MAOIs has been raised up by several studies investigating role MAOs, particularly tumor insurgence progression, efficacy coadjutants therapy chemoresistant tumors....
A new series of 3-, 4-, 7-polysubstituted coumarins have been designed and evaluated for their monoamine oxidase B (MAO-A MAO-B) inhibitory potency. Substituents at position 7 consisted a bridge different physicochemical nature linking phenyl ring to the coumarin scaffold. Structure−affinity structure−selectivity relationships, derived through CoMFA-GOLPE docking studies, revealed key interactions responsible observed MAO-B MAO-A potency suggested main structural determinants high...