| Title : Design, synthesis, in vitro and in vivo evaluation of benzylpiperidine-linked 1,3-dimethylbenzimidazolinones as cholinesterase inhibitors against Alzheimer's disease - Mo_2020_J.Enzyme.Inhib.Med.Chem_35_330 |
| Author(s) : Mo J , Chen T , Yang H , Guo Y , Li Q , Qiao Y , Lin H , Feng F , Liu W , Chen Y , Liu Z , Sun H |
| Ref : J Enzyme Inhib Med Chem , 35 :330 , 2020 |
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Abstract :
Cholinesterase inhibitor plays an important role in the treatment of patients with Alzheimer's disease (AD). Herein, we report the medicinal chemistry efforts leading to a new series of 1,3-dimethylbenzimidazolinone derivatives. Among the synthesised compounds, 15b and 15j showed submicromolar IC50 values (15b, eeAChE IC50 = 0.39 +/- 0.11 microM; 15j, eqBChE IC50 = 0.16 +/- 0.04 microM) towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Kinetic and molecular modelling studies revealed that 15b and 15j act in a competitive manner. 15b and 15j showed neuroprotective effect against H2O2-induced oxidative damage on PC12 cells. This effect was further supported by their antioxidant activity determined in a DPPH assay in vitro. Morris water maze test confirmed the memory amelioration effect of the two compounds in a scopolamine-induced mouse model. Moreover, the hepatotoxicity of 15b and 15j was lower than tacrine. In summary, these data suggest 15b and 15j are promising multifunctional agents against AD. |
| PubMedSearch : Mo_2020_J.Enzyme.Inhib.Med.Chem_35_330 |
| PubMedID: 31856607 |
Mo J, Chen T, Yang H, Guo Y, Li Q, Qiao Y, Lin H, Feng F, Liu W, Chen Y, Liu Z, Sun H (2020)
Design, synthesis, in vitro and in vivo evaluation of benzylpiperidine-linked 1,3-dimethylbenzimidazolinones as cholinesterase inhibitors against Alzheimer's disease
J Enzyme Inhib Med Chem
35 :330
Mo J, Chen T, Yang H, Guo Y, Li Q, Qiao Y, Lin H, Feng F, Liu W, Chen Y, Liu Z, Sun H (2020)
J Enzyme Inhib Med Chem
35 :330