1. Design and Development of Multifunctional Hybrids of Ferulic Acid and 1,3,4-Oxadiazoles for the Treatment of Alzheimer's Disease.
- Author
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Tripathi, Avanish, Choubey, Priyanka Kumari, Seth, Ankit, Sharma, Piyoosh, Tripathi, Manish Kumar, and Shrivastava, Sushant Kumar
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FERULIC acid , *ALZHEIMER'S disease , *BLOOD-brain barrier , *PROPIDIUM iodide , *MOLECULAR docking , *BINDING sites - Abstract
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 4- hydroxy-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. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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