Identification of the most potent acetylcholinesterase inhibitors from plants for possible treatment of Alzheimer’s disease: a computational approach

Abstract

Background Being one of the rapidly growing dementia type diseases in the world, Alzheimer’s disease (AD) has gained much attention from researchers in the recent decades. Many hypotheses have been developed that describe different reasons for the development of AD. Among them, the cholinergic hypothesis depicts that the degradation of an important neurotransmitter, acetylcholine by the enzyme acetylcholinesterase (AChE), is responsible for the development of AD. Although, many anti-AChE drugs are already available in the market, their performance sometimes yields unexpected results. For this reason, research works are going on to find out potential anti-AChE agents both from natural and synthetic sources. In this study, 50 potential anti-AChE phytochemicals were analyzed using numerous tools of bioinformatics and in silico biology to find out the best possible anti-AChE agents among the selected 50 ligands through molecular docking, determination of the druglikeness properties, conducting the ADMET test, PASS and P450 site of metabolism prediction, and DFT calculations. Result The predictions of this study suggested that among the selected 50 ligands, bellidifolin, naringenin, apigenin, and coptisine were the 4 best compounds with quite similar and sound performance in most of the experiments. Conclusion In this study, bellidifolin, naringenin, apigenin, and coptisine were found to be the most effective agents for treating the AD targeting AChE. However, more in vivo and in vitro analyses are required to finally confirm the outcomes of this research.

In-Silico Molecular Docking and Pharmaco-Kinetic Activity Analysis of Potential Inhibitors against SARS-CoV-2 Spike Glycoproteins

“…Larger Gap value suggests the hardness of the drug molecules, which is closely associated with the lower chemical reactivity and high kinetic stability. The smaller Gap value indicates the softness of the drug molecules, which signifies low kinetic stability and high chemical reactivity [60][61][62]. All the drugs in this study exhibit lower (<1.3) HOMO-LUMO GAP, indicating high chemical reactivity of the drugs described in Table 6.…”

Soyasapogenol-B as a Potential Multitarget Therapeutic Agent for Neurodegenerative Disorders: Molecular Docking and Dynamics Study

“…AChE is a key enzyme of the cholinergic system, and has been reported to be deteriorated in the progression of AD, which is accompanied by the decline of acetylcholine and the loss of cholinergic neurons in the forebrain. There are multiple therapeutic modalities targeting the cholinergic system; in particular, AChE is the main target that has been proven to be a promising therapeutic strategy [30]. BuChE is a serine hydrolase enzyme that plays a crucial role in the regulation of acetylcholine metabolism, and is closely related to AChE.…”

Investigation of Excellent ACE Inhibitor Agents from Scurrula atropurpure and Dendrophthoe pentandra for Anti-Hypertension

“…Theoretically, the application of the methods of virtual screening is limited to the structures of the compounds that can be counted and to compounds known to have ties with other compounds. There are a lot of studies doing computer screening and active compound molecular docking to a target protein (Kumar, et al, 2017;Mubarakati, et al, 2019;Sarkar, et al, 2021). Nevertheless, these predictive results require validation through in vitro and in vivo toxicological and pharmacological assays and experimental bioavailability tests for this main compound concerning hypertension prevention.…”