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

[ Vol. 24 , Issue. 5 ]

Author(s):

Richa Arya*, Sarvesh Paliwal, S.P Gupta, Swapnil Sharma, Kirtika Madan, Achal Mishra, Kanika Verma and Neha Chauhan   Pages 729 - 736 ( 8 )

Abstract:


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.

Affiliation:

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, Banasthali Vidyapith, Banasthali-304022 (Raj.), Banasthali Vidyapith, Banasthali-304022 (Raj.)



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