Alzheimer's disease (AD) is a chronic neurodegenerative disease of the elderly that seriously affects the quality of life and the life expectancy of those affected. There is, as yet, no effective drug treatment of AD, although several acetylcholinesterase (AChE) inhibitors and a glutamate antagonist can provide relief from its symptoms. Recent studies have indicated that the overactivation of poly(ADP-ribose) polymerase-1 (PARP-1) may promote nerve cell death in the brains of AD patients, implying that PARP-1 inhibition may have therapeutic value for the treatment of AD. Therefore, it is important to investigate novel agents with both AChE- and PARP-1-inhibitory bioactivities. In this study, the structure-based virtual screening of PARP-1 inhibitors was performed to search for potential agents with high affinities for AChE. The dynamic stability of the selected AChE-ligand complexes was investigated by molecular dynamics (MD) simulation. Two compounds, CID57390505 and CID71605390, showed high affinities for and stability in complex with AChE in docking and MD simulations. Thus, our in silico research identified two compounds with AChE and PARP-1 dual-targeted activities, indicating that this technique could aid attempts to develop more potent agents against AD.
[1]Shanghai Univ Med & Hlth Sci, Coll Pharm, Shanghai, Peoples R China.
[2]Wuhan Univ Sci & Technol, Dept Pharm, Coll Med, Wuhan, Hubei, Peoples R China.
[3]Wuhan Univ Sci & Technol, Hubei Prov Key Lab Occupat Hazard Identificat & C, Wuhan, Hubei, Peoples R China.
[4]Wuhan Univ Sci & Technol, New Drugs Innovat & Dev Inst, Dept Pharm, Coll Med, Wuhan, Hubei, Peoples R China.
(8.0+极速模式)