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In-silico Studies and Biological Activity of Potential BACE-1 Inhibitors


Richa Arya*, Sarvesh Paliwal, S.P Gupta, Swapnil Sharma, Kirtika Madan, Achal Mishra, Kanika Verma and Neha Chauhan   Pages 1 - 8 ( 8 )


Background: Alzheimer’s disease is neurological condition causing cognitive inability and dementia. The pathological lesions and neuronal damage in brain is 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.

Method: A QSAR study was performed on 55 Pyrrolidine based ligands as BACE-1 inhibitors with activity magnitude of greater than 4.of compounds.

Results: In an advent to design 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 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 highest fit value and docking score. The biological activity evaluation by in-vitro assay was found to be >0.1µM.


BACE-1, Docking, In-silico, Pharmacophore, Secretase. BACE-1, Secretase


Banasthali Vidyapith, Banasthali-304022 (Raj.), Banasthali Vidyapith, Banasthali-304022 (Raj.), Department of Pharmaceutical Technology, Meerut Institute of Engineering and Technology, Meerut-250005, Banasthali Vidyapith, Banasthali-304022 (Raj.), Banasthali Vidyapith, Banasthali-304022 (Raj.), Faculty of pharmaceutical sciences, Shri Shankaracharya Tech. Campus. Bhilai, Chhattisgarh, Banasthali Vidyapith, Banasthali-304022 (Raj.), Banasthali Vidyapith, Banasthali-304022 (Raj.)

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