Synthesis and Biological Evaluation of 1,3,4-Oxadiazole Derivatives as Acetylcholinesterase Inhibitors

• Published in: Russian journal of organic chemistry Vol. 58; no. 10; pp. 1520 - 1526
• Main Authors: Yang, Shun, Zou, Jing-Pei, Li, Xiang-Rong, Li, Rui, Qian, Jing-Jing, Wu, Wen-Long, Su, Jia-Bin, Chen, Ke-Qi, Qin, Tian, Liu, Shan-Ming, Liu, Wei-Wei, Shi, Da-Hua
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01.10.2022; Springer Nature; Springer Nature B.V
• Subjects: Amino acids; Chemistry; Chemistry and Materials Science; Chemistry, Organic; Inhibitors; Mass spectra; Molecular docking; NMR; Nuclear magnetic resonance; Organic Chemistry; Oxadiazoles; Physical Sciences; Science & Technology; Synthesis; derivatives; acetylcholinesterase; Alzheimer’s disease; 1,3,4-oxadiazole; Alzheimer's disease; BINDING
• ISSN: 1070-4280; 1608-3393
• DOI: 10.1134/S1070428022100207

A series of 1,3,4-oxadiazole derivatives were designed, synthesized, and evaluated as acetylcholin­esterase inhibitors. Their structure was confirmed by IR, NMR, and high-resolution mass spectra. The syn­thesized compounds showed significant acetylcholinesterase inhibitory activity with an IC 50 value of 0.07 μM for the most potent compound. Molecular docking study of the most active compound indicated that it interacted with the crucial amino acids present at the catalytic active site and peripheral anionic site of acetylcholinesterase. The results suggested that the obtained 1,3,4-oxadiazole derivatives may be the potential drug candidates for the treatment of Alzheimer’s disease as AChE inhibitors.