A5039559658- Cholinesterase and Neurodegenerative Diseases
- Computational Drug Discovery Methods
- Alzheimer's disease research and treatments
- Medicinal Plants and Neuroprotection
- Poisoning and overdose treatments
- Venomous Animal Envenomation and Studies
- Pharmacogenetics and Drug Metabolism
- Receptor Mechanisms and Signaling
- Metabolism and Genetic Disorders
- Nutrition, Genetics, and Disease
- Genomics and Rare Diseases
- Plant-based Medicinal Research
- Biochemical Acid Research Studies
- Redox biology and oxidative stress
- Electrochemical sensors and biosensors
- Chemical synthesis and alkaloids
University of Bari Aldo Moro
2014-2018
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...
The need for developing real disease-modifying drugs against neurodegenerative syndromes, particularly Alzheimer's disease (AD), shifted research towards reliable drug discovery strategies to unveil clinical candidates with higher therapeutic efficacy than single-targeting drugs. By following the multi-target approach, we designed and synthesized a novel class of dual acetylcholinesterase (AChE)-monoamine oxidase B (MAO-B) inhibitors through decoration 2H-chromen-2-one skeleton. Compounds...
Acetylcholinesterase (AChE) inhibitors still comprise the majority of marketed drugs for Alzheimer's disease (AD). The structural arrangement enzyme, which features a narrow gorge that separates catalytic and peripheral anionic subsites (CAS PAS, respectively), inspired development bivalent ligands are able to bind block activity CAS as well role PAS in beta amyloid (Aβ) fibrillogenesis. With aim discovering novel AChE dual binders with improved drug-likeness, homo- heterodimers containing...