2. Academic Validation
  3. Emergence of a Potent AChE Inhibitor with Antioxidant and Neuroprotection Abilities

Emergence of a Potent AChE Inhibitor with Antioxidant and Neuroprotection Abilities

  • ACS Med Chem Lett. 2025 Dec 26;17(1):137-143. doi: 10.1021/acsmedchemlett.5c00524.
Alsiddig Osama 1,  Miaomiao Ji 2,  Jianguo Fang 1 3,  Haiyu Zhao 2,  Baoxin Zhang 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Product Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.
  • 2 Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, Lanzhou University, Lanzhou 730000, China.
  • 3 School of Chemistry and Chemical Engineering, Nanjing University of Science & Technology, Nanjing, Jiangsu 210094, China.
PMID: 41531953 DOI: 10.1021/acsmedchemlett.5c00524
Abstract

Oxidative damage and cholinergic dysfunction are common pathological features of Alzheimer's disease (AD). Maintaining the redox balance of neurons and cholinergic signaling through Antioxidants and acetylcholinesterase (AChE) inhibition may provide therapeutic benefits for AD. In this regard, we discovered three AChE inhibitors with more potency than the positive control (rivastigmine; IC50 = 24.5 μM). Among these active compounds, C5 (a flavonoid derivative) was the most potent AChE Inhibitor with an IC50 of 5.02 μM, followed by C1, C6, and C2 with IC50 values of 7.94 μM, 8.13 μM, and 27.52 μM, respectively. Compound C5 also demonstrated strong neuroprotective activity, rescuing PC12 cells from H2O2-induced damage and scavenging various ROS models. Interestingly, C5 also prevented memory impairments in the scopolamine-induced cognitive dysfunction zebrafish model. Our findings suggest that C5 is a potential drug lead for cholinergic dysfunction-related disorders such as AD.

Keywords

Alzheimer’s disease; acetylcholinesterase; antioxidant; neuroprotection.

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