Multitarget-directed benzylideneindanone derivatives: anti-beta-amyloid (Abeta) aggregation, antioxidant, metal chelation, and monoamine oxidase B (MAO-B) inhibition properties against Alzheimer's disease.
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Huang L, Lu C, Sun Y, Mao F, Luo Z, Su T, Jiang H, Shan W, Li X
Multitarget-directed benzylideneindanone derivatives: anti-beta-amyloid (Abeta) aggregation, antioxidant, metal chelation, and monoamine oxidase B (MAO-B) inhibition properties against Alzheimer's disease.
J Med Chem. 2012 Oct 11;55(19):8483-92. doi: 10.1021/jm300978h. Epub 2012 Oct 1.
- PubMed ID
- 22978824 [ View in PubMed]
- Abstract
A novel series of benzylideneindanone derivatives were designed, synthesized, and evaluated as multitarget-directed ligands against Alzheimer's disease. The in vitro studies showed that most of the molecules exhibited a significant ability to inhibit self-induced beta-amyloid (Abeta(1-42)) aggregation (10.5-80.1%, 20 muM) and MAO-B activity (IC(50) of 7.5-40.5 muM), to act as potential antioxidants (ORAC-FL value of 2.75-9.37), and to function as metal chelators. In particular, compound 41 had the greatest ability to inhibit Abeta(1-42) aggregation (80.1%), and MAO-B (IC(50) = 7.5 muM) was also an excellent antioxidant and metal chelator. Moreover, it is capable of inhibiting Cu(II)-induced Abeta(1-42) aggregation and disassembling the well-structured Abeta fibrils. These results indicated that compound 41 is an excellent multifunctional agent for the treatment of AD.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Clorgiline Amine oxidase [flavin-containing] A IC 50 (nM) 4.1 N/A N/A Details Rasagiline Amine oxidase [flavin-containing] B IC 50 (nM) 14 N/A N/A Details Selegiline Amine oxidase [flavin-containing] A IC 50 (nM) 70200 N/A N/A Details Selegiline Amine oxidase [flavin-containing] B IC 50 (nM) 18.5 N/A N/A Details