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Research Paper | Chemistry | Sri Lanka | Volume 12 Issue 9, September 2023
In Silico Study of Natural Product Inhibitors of AChE and their Potential Therapeutic Value for the Cholinergic Hypothesis in the Development of Alzheimer's Disease
D.S.P.C.N de Silva
Abstract: The most prevalent cause of dementia in elderly persons is Alzheimer's Disease (AD), which is characterized by a progressive deterioration in cognitive function as a result of brain damage. The cholinergic system anomalies are the most severely affected. As cholinergic deficits could be treated by reversibly inhibiting the acetylcholinesterase (AChE) enzyme, inhibition of AChE has become one of the most promising therapy options for AD. The main goal of this study is to investigate the natural product inhibitors of AChE and their potential therapeutic value for the cholinergic hypothesis in the development of AD using molecular docking approach. The crystal structure of hAChE; PDB entry: 6O4W was used in this study. Ten selected drug candidates including Ginsensoside, Apigenin, Curcumin, Mangiferin, Galantamine, Resveratrol, Rivastigmine, Ribalinine, Caranine, and tazettine were docked in order to determine their binding affinities using Avagadro, pYrX, and Discovery Studio 2019 Client software. The bioavailability of the drugs was assessed by using swissADME web server obtaining bioavailability radar and pharmacokinetics was evaluated using protox web server. Then their recent progress in drug development in relation to their properties was discussed in the study. According to the Binding affinities of the inhibitors Apigenin, Ginsensoside, Curcumin, and Caranine showed the highest potential for inhibitory activity respectively. The re docking results showed that the conformation of the docked ligand sufficiently matches with the original ligand; hence the docking protocol was validated.
Keywords: cholinergic hypothesis, acetylcholinesterase (AChE) inhibitors, natural product inhibitors of AChE, molecular docking
Edition: Volume 12 Issue 9, September 2023,
Pages: 1616 - 1619