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New Coumarin Derivatives as Cholinergic and Cannabinoid System Modulators
Serena Montanari1, Marco Allarà2, Laura Scalvini3
1Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
Molecules (Basel, Switzerland)
|June 2, 2021
Summary
New coumarin derivatives show potential for Alzheimer's disease treatment by targeting the endocannabinoid system and cholinergic pathways. These compounds inhibit key enzymes and protein aggregation, offering a multitarget approach for neuroprotection.
Area of Science:
- Medicinal Chemistry
- Neuroscience
- Pharmacology
Background:
- The endocannabinoid system (eCS) plays a role in neuroprotection, cognitive function, and Alzheimer's disease (AD) pathophysiology.
- Targeting the eCS offers a potential therapeutic strategy for AD, necessitating the development of multitarget agents.
Purpose of the Study:
- To design and synthesize novel coumarin-based carbamic and amide derivatives as potential multitarget agents for AD.
- To evaluate the synthesized compounds' activity against cholinergic targets and eCS-related pathways.
Main Methods:
- Synthesis of coumarin-based carbamic and amide derivatives.
- Enzymatic assays to assess inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and fatty acid amide hydrolase (FAAH).
- Evaluation of binding affinity for cannabinoid receptors (CB1 and CB2) and assessment of beta-amyloid (Aβ42) self-aggregation inhibition.
Main Results:
- Compounds 2 and 3, carbamate derivatives, showed promising inhibition of human AChE (hAChE), human BuChE (hBuChE), FAAH, and Aβ42 self-aggregation.
- Amide derivative 6 demonstrated potential as a CB1/CB2 receptor ligand.
- The synthesized compounds exhibited a multitarget profile with encouraging neuroprotective potential.
Conclusions:
- The novel coumarin-based compounds possess a promising multitarget profile for Alzheimer's disease therapy.
- Further investigation is warranted to optimize these agents for enhanced therapeutic efficacy in neurodegenerative diseases.
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