Dual functional cholinesterase and MAO inhibitors for the treatment of Alzheimer's disease: synthesis, pharmacological analysis and molecular modeling of homoisoflavonoid derivatives. (3rd May 2016)

• Record Type: Journal Article
• Authors: Wang, Yali; Sun, Yang; Guo, Yueyan; Wang, Zechen; Huang, Ling; Li, Xingshu
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 31:Number 3(2016:Jun.)
• Page Start: 389
• Page End: 397
• Publication Date: 2016-05-03
• Subjects: Alzheimer's disease -- cholinesterase inhibitors -- homoisoflavonoid derivatives -- MAO inhibitors; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.3109/14756366.2015.1024675
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: Because of the complexity of Alzheimer's disease (AD), the multi-target-directed ligand (MTDL) strategy is expected to provide superior effects for the treatment of AD, instead of the classic one-drug-one-target strategy. In this context, we focused on the design, synthesis and evaluation of homoisoflavonoid derivatives as dual acetyl cholinesterase (AChE) and monoamine oxidase (MAO-B) inhibitors. Among all the synthesized compounds, compound10 provided a desired balance of AChE and hMAO-B inhibition activities, with IC50 value of 3.94 and 3.44 μM, respectively. Further studies revealed that compound10 was a mixed-type inhibitor of AChE and an irreversible inhibitor of hMAO-B, which was also confirmed by molecular modeling studies. Taken together, the data indicated that10 was a promising dual functional agent for the treatment of AD.