Pyrazolines as potential anti-Alzheimer's agents: DFT, molecular docking, enzyme inhibition and pharmacokinetic studies

RSC Medicinal Chemistry
2022.0

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease that is characterized as the main dementia in the elderly. Eighteen pyrazolines were synthesized and evaluated for their inhibitory effects against acetylcholinesterase (AChE) <i>in vitro</i>. Possible interactions between pyrazolines and the enzyme were explored by <i>in silico</i> experiments. Compound 2B of the series was the most active pyrazoline with an IC<sub>50</sub> value of 58 nM. Molecular docking studies revealed two important π-π interactions with residues Trp 286 and Tyr 341. A correlation between the HOMO-1 surface and AChE inhibition was observed. ADMET assays demonstrated a good profile for compound 2B. From the abovementioned findings, a new avenue of compound 2B analogues could be explored to develop anti-AD agents.

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