Resveratrol-maltol hybrids as multi-target-directed agents for Alzheimer's disease
Gang Cheng1, Ping Xu2, Minkui Zhang3
1College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou 311402, PR China; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, PR China.
Bioorganic & Medicinal Chemistry
|October 27, 2018
Summary
New resveratrol-maltol hybrids show promise for Alzheimer's disease by inhibiting amyloid-beta aggregation, acting as antioxidants, and chelating metals. Compounds 8i and 8j exhibit significant potential in early evaluations.
Area of Science:
- Medicinal Chemistry
- Neuroscience
- Biochemistry
Background:
- Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) aggregation.
- Resveratrol and maltol are known for their antioxidant and metal chelating properties.
- Multi-target-directed ligands (MTDLs) offer a promising therapeutic strategy for complex diseases like AD.
Purpose of the Study:
- To synthesize novel resveratrol-maltol hybrids as potential MTDLs for AD.
- To evaluate the in vitro biological activities of these hybrids, focusing on Aβ aggregation inhibition, antioxidant capacity, and metal chelation.
Main Methods:
- Synthesis of a series of resveratrol-maltol hybrids (compounds 8a-8k).
- In vitro assessment of Aβ1-42 self-induced aggregation inhibition.
- Evaluation of antioxidant activity using ABTS+ radical scavenging assay.
- Assessment of metal chelating properties.
Main Results:
- The synthesized resveratrol-maltol hybrids demonstrated a triple function: inhibition of Aβ1-42 aggregation, antioxidant activity, and metal chelation.
- Compounds 8i and 8j exhibited significant potential, showing micromolar IC50 values for Aβ1-42 aggregation inhibition.
- Compounds 8i and 8j displayed superior ABTS+ radical scavenging activity compared to Trolox and demonstrated good metal chelating capabilities.
Conclusions:
- Resveratrol-maltol hybrids represent a novel class of MTDLs with potential therapeutic applications for Alzheimer's disease.
- Compounds 8i and 8j are particularly promising candidates due to their potent Aβ aggregation inhibitory, antioxidant, and metal chelating activities.
- Further investigation into these hybrids could lead to the development of new strategies for AD treatment.
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