Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology, (Banaras Hindu University), Varanasi, 221005, India
*For Correspondence - skshrivastava.phe@itbhu.ac.in
Online published on 27 August, 2020.
Ferulic acid-based multifunctional molecular hybrids of 1,3,4-oxadiazoles were designed, synthesized, and biologically evaluated for the treatment of Alzheimer's disease. Among the synthesized compounds, the derivatives with 4hydroxy-3,5-dimethoxy substituent (FA5 and CFA5) showed balanced inhibitory potential against hAChE, hBChE, and hBACE-1. Also, CFA5displayed remarkable PAS-AChE binding with significant displacement of propidium iodide, and appreciable blood-brain barrier permeability predictions in PAMPA-BBB assay. The thioflavin T assay in self- and AChE-induced experiments established the considerable anti-Aâ aggregatory activity of CFA5. Compound CFA5 also showed neuroprotective activity in Aâ-induced oxidative stress against SH-SY5Y neuroblastoma cell lines. Moreover,in vivo behavioral studies showed amelioration of cognitive dysfunction in rats tested by Y-maze. In silico molecular docking study showed consensual binding interactions of CFA5 with active binding site residues of AChE and BACE-1.
Alzheimer's disease, Acetylcholinesterase (AChE), â-secretase-1 (BACE-1), Aâ, Aggregation;molecular hybridization, Multifunctional agents
