3353-15-9Relevant academic research and scientific papers
Computational exploration and experimental validation to identify a dual inhibitor of cholinesterase and amyloid-beta for the treatment of Alzheimer’s disease
Seth, Ankit,Sharma, Piyoosh,Shrivastava, Sushant Kumar,Srivastava, Pavan,Tripathi, Avanish,Tripathi, Manish Kumar,Tripathi, Prabhash Nath
, (2020)
The cholinesterases are essential targets implicated in the pathogenesis of Alzheimer’s disease (AD). In the present study, virtual screening and molecular docking are performed to identify the potential hits. Docking-post processing (DPP) and pose filtration protocols against AChE and BChE resulted in three hits (AW00308, HTS04089, and JFD03947). Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) and molecular dynamics simulation analysis affirmed the stability and binding pattern of the docked complex JFD03947, which was further synthesized and evaluated for in vitro cholinesterase inhibition (AChE, IC50 = 0.062 μM; BChE, IC50 = 1.482 μM) activity. The enzyme kinetics study of the JFD03947 against hAChE and hBChE suggested a mixed type of inhibition. The results of thioflavin T-assay also elicited anti-Aβ aggregation activity by JFD03947. Further, biological evaluation of identified compound JFD03947 also showed neuroprotective ability against the SH-SY5Y neuroblastoma cell lines.
