| Title : Dual functional cholinesterase and MAO inhibitors for the treatment of Alzheimer's disease: synthesis, pharmacological analysis and molecular modeling of homoisoflavonoid derivatives - Wang_2016_J.Enzyme.Inhib.Med.Chem_31_389 |
| Author(s) : Wang Y , Sun Y , Guo Y , Wang Z , Huang L , Li X |
| Ref : J Enzyme Inhib Med Chem , 31 :389 , 2016 |
|
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 muM, 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. |
| PubMedSearch : Wang_2016_J.Enzyme.Inhib.Med.Chem_31_389 |
| PubMedID: 25798687 |
Wang Y, Sun Y, Guo Y, Wang Z, Huang L, Li X (2016)
Dual functional cholinesterase and MAO inhibitors for the treatment of Alzheimer's disease: synthesis, pharmacological analysis and molecular modeling of homoisoflavonoid derivatives
J Enzyme Inhib Med Chem
31 :389
Wang Y, Sun Y, Guo Y, Wang Z, Huang L, Li X (2016)
J Enzyme Inhib Med Chem
31 :389