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Chemoselective Modification of Viral Surfaces via Bioorthogonal Click Chemistry
Published on: August 19, 2012
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First Sustainable One-Pot Tandem Hantzsch Multicomponent Reaction/Click Reaction Approach for Novel
Paul J Bernard1, Anna Więckowska2, Sylvain Grosjean1
1Univ. Marie et Louis Pasteur, UMR INSERM 1322 LINC, 19 rue Ambroise Paré, F-25000 Besançon, France.
ACS Chemical Neuroscience
|December 29, 2025
Summary
Novel drug candidates for Alzheimer's disease (AD) were developed using a green chemistry approach. Compounds DHP IIIj and IIIk showed promise in reversing memory loss in mice, offering new therapeutic potential.
Area of Science:
- Medicinal Chemistry
- Neuroscience
- Green Chemistry
Background:
- Alzheimer's disease (AD) poses a significant therapeutic challenge, necessitating innovative treatment strategies.
- Multitarget-directed ligands (MTDLs) offer a promising approach by simultaneously addressing multiple pathological pathways in AD.
- Dihydropyridines (DHPs) and tacrine are known for their neuroprotective and cholinesterase inhibitory activities, respectively.
Purpose of the Study:
- To design and synthesize novel MTDLs combining DHP and tacrine moieties for potential AD treatment.
- To evaluate the synthesized compounds for anticholinesterase, antioxidant, neuroprotective, and calcium channel inhibitory activities.
- To assess the antiamnesic efficacy of the lead compounds in a preclinical mouse model.
Main Methods:
- A novel one-pot tandem Hantzsch multicomponent/click reaction was employed for the synthesis of 18 DHP derivatives (IIIa-r).
- The synthesized compounds were characterized using standard analytical techniques.
- In vitro assays were performed to evaluate enzyme inhibition and antioxidant properties.
- In vivo studies using scopolamine-induced amnesia in mice were conducted to assess antiamnesic effects.
Main Results:
- Eighteen novel DHP derivatives were successfully synthesized via a sustainable one-pot tandem reaction.
- Compounds DHP IIIj and IIIk exhibited significant multitarget activities, including anticholinesterase and neuroprotective effects.
- DHP IIIj and IIIk demonstrated significant antiamnesic properties by reversing scopolamine-induced memory impairment in mice.
Conclusions:
- The developed one-pot tandem synthesis represents a green and efficient method for generating MTDLs for AD.
- DHP IIIj and IIIk show considerable promise as innovative therapeutic candidates for Alzheimer's disease.
- The study validates the MTDL strategy and highlights the potential of these novel compounds in AD treatment.
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