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Multifunctional indanone–chalcone hybrid compounds with anti-β-amyloid (Aβ) aggregation, monoamine oxidase B (MAO-B) inhibition and neuroprotective properties against Alzheimer’s disease
- Source :
- Medicinal Chemistry Research. 28:1912-1922
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- To discover multifunctional agents for the treatment of Alzheimer’s disease (AD), a series of indanone–chalcone hybrid compounds were designed and synthesized based on the multitarget-directed ligand strategy. Their monoamino oxidases (MAO-A and MAO-B) and Aβ1–42 aggregation inhibitory activities were evaluated. The results were shown that all synthetic compounds exhibited mostly good multifunctional activities. Among all, compound TM-11 represented the best Aβ1–42 aggregation inhibitory potency (IC50 ~1.8 μM) and good disaggregation activity (IC50 ~7.9 μM). Both TEM images and docking studies provided good reasonable explanation to the hypothesis. Meanwhile, compound TM-11 was a selective MAO-B inhibitor, as well as a neuroprotective agent against Aβ1–42-induced toxicity. Based on the structural considerations, the lipophilicity of the compound TM-11 could render to pass through blood−brain barrier (BBB) in vitro in accordance with the Lipinski’s rule of five. In conclusion, these results were suggested that compound TM-11 might be a potential multifunctional agent for the treatment of AD.
Details
- ISSN :
- 15548120 and 10542523
- Volume :
- 28
- Database :
- OpenAIRE
- Journal :
- Medicinal Chemistry Research
- Accession number :
- edsair.doi...........a816408907df0c189249b2ecdbe756c2