Background: Alzheimer’s disease is a neurological condition causing cognitive inability
and dementia. The pathological lesions and neuronal damage in the brain are caused by self-aggregated
fragments of mutated Amyloidal precursor protein (APP).
Objective: The controlled APP processing by inhibition of secretase is the strategy to reduce Aβ
load to treat Alzheimer’s disease.
Methods: A QSAR study was performed on 55 Pyrrolidine based ligands as BACE-1 inhibitors
with an activity magnitude greater than 4 of compounds.
Results: In the advent of designing new BACE-1 inhibitors, the pharmacophore model with correlation
(r = 0.90) and root mean square deviation (RMSD) of 0.87 was developed and validated. Further,
the hits retrieved by the in-silico approach were evaluated by docking interactions.
Conclusion: Two structurally diverse compounds exhibited Asp32 and Thr232 binding with the
BACE-1 receptor. The aryl-substituted carbamate compound exhibited the highest fit value and
docking score. The biological activity evaluation by in-vitro assay was found to be >0.1μM.
Keywords: BACE-1, docking, In-silico, pharmacophore, secretase, secretase. BACE-1.
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