title: Dual functional cholinesterase and MAO inhibitors for the treatment of Alzheimer's disease: synthesis, pharmacological analysis and molecular modeling of homoisoflavonoid derivatives.
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, compound 10 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 compound 10 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 that 10 was a promising dual functional agent for the treatment of AD.
authors: a School of Pharmaceutical Sciences, Institute of Drug Synthesis and Pharmaceutical Process, Sun Yat-sen University , Guangzhou , China.
authors: Yali
authors: Y
authors: Wang
authors: a School of Pharmaceutical Sciences, Institute of Drug Synthesis and Pharmaceutical Process, Sun Yat-sen University , Guangzhou , China.
authors: Yang
authors: Y
authors: Sun
authors: a School of Pharmaceutical Sciences, Institute of Drug Synthesis and Pharmaceutical Process, Sun Yat-sen University , Guangzhou , China.
authors: Yueyan
authors: Y
authors: Guo
authors: a School of Pharmaceutical Sciences, Institute of Drug Synthesis and Pharmaceutical Process, Sun Yat-sen University , Guangzhou , China.
authors: Zechen
authors: Z
authors: Wang
authors: a School of Pharmaceutical Sciences, Institute of Drug Synthesis and Pharmaceutical Process, Sun Yat-sen University , Guangzhou , China.
authors: Ling
authors: L
authors: Huang
authors: a School of Pharmaceutical Sciences, Institute of Drug Synthesis and Pharmaceutical Process, Sun Yat-sen University , Guangzhou , China.
authors: Xingshu
authors: X
authors: Li
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002802:Cholinesterases / Q000378:metabolism; D007529:Isoflavones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002800:Cholinesterase Inhibitors; D007529:Isoflavones; D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase; D002802:Cholinesterases
keywords: Alzheimer’s disease; MAO inhibitors; cholinesterase inhibitors; homoisoflavonoid derivatives