Sulfonamides as multifunctional agents for Alzheimer's disease
Seema Bag1, Rekha Tulsan1, Abha Sood1
1Department of Chemistry, University of Massachusetts Boston, 100 Morrissey Blvd., Boston, MA, USA.
Bioorganic & Medicinal Chemistry Letters
|December 25, 2014
Summary
New sulfonamide-based compounds were developed as potential Alzheimer's disease treatments. These agents inhibit amyloid-beta self-assembly, modulate cholinesterase activity, and scavenge free radicals, showing promise for multi-target drug design.
Area of Science:
- Medicinal Chemistry
- Neuroscience
- Pharmacology
Background:
- Alzheimer's disease (AD) pathology involves complex processes including amyloid-beta (Aβ) self-assembly, cholinesterase activity, and oxidative stress.
- Multifunctional agents offer a promising therapeutic strategy by targeting multiple pathological pathways simultaneously.
Purpose of the Study:
- To design and synthesize novel sulfonamide linker-based inhibitors with extended linear structures.
- To evaluate the inhibitory potential of these compounds against Aβ self-assembly, cholinesterase activity, and free radical scavenging.
Main Methods:
- Synthesis of sulfonamide linker-based compounds with extended linear scaffolds.
- Biochemical assays to assess inhibition of Aβ fibril and oligomer formation.
- Enzyme inhibition assays for acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE).
- Free radical scavenging assays to evaluate antioxidant properties.
Main Results:
- Several synthesized compounds demonstrated significant inhibition of Aβ self-assembly.
- Compounds also showed effective modulation of cholinesterase (AChE and BuChE) activity.
- Promising free radical scavenging properties were observed in parallel with other activities.
Conclusions:
- The study identified three lead compounds (14, 19, and 26) with multifunctional potential for Alzheimer's disease therapy.
- Sulfonamide linker-based scaffolds are effective for developing multi-target agents against AD.
- Further optimization of these leads could lead to novel drug candidates for Alzheimer's disease.
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