In silico and in vitro anti-AChE activity investigations of constituents from Mytragyna speciosa for Alzheimer’s disease treatment

Innok, Wansiri; Hiranrat, Asadhawut; Chana, Netnapa; Rungrotmongkol, Thanyada; Kongsune, Panita

doi:10.1007/s10822-020-00372-4

Cited by 11 publications

(9 citation statements)

References 40 publications

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“…Considering the free energy combined with solvation free energy, the polar term (Δ𝐺 ele,solv + Δ𝐸 ele ) was an unfavorable contribution, which was determined to a large extent by desolvation energy with relatively high positive values of polar solvation resulting from either PB or GB models in both complexes. This phenomenon has been also found in some biological systems in an aqueous solution, where the binding pocket of enzyme is a hydrophobic cavity [46,47]. On the other hand, the nonpolar solvation term (Δ𝐺 nonpolar,solv + Δ𝐸 vdW ) showed more favorable contribution to the total binding free energies in both complexes.…”

Section: Binding Free Energy Calculationssupporting

confidence: 63%

Structural Dynamics and Susceptibility of Anti-Alzheimer’s Drugs Donepezil and Galantamine against Human Acetylcholinesterase

Nutho

Yanarojana²,

Supavilai³

2022

Trends Sci

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Alzheimer’s disease (AD) is a major public health problem worldwide due to an increase in the elderly population. The current pharmacotherapy for the early stages of AD is mainly dependent on cholinesterase inhibitors. Two of the most commonly used anti-AD drugs, donepezil (DPZ) and galantamine (GLM), are selective inhibitors for human acetylcholinesterase (hAChE). However, the inhibitory activity of DPZ on hAChE was more potent than GLM by ~85 times. To better understand the molecular basis for differences in mode of inhibition of hAChE by both drugs, molecular dynamics (MD) simulation was performed. The results showed that the active site residues of hAChE/DPZ had the higher hydrogen bond occupancies as compared to hAChE/GLM. Nevertheless, the 2 drugs directly formed hydrogen bonds with the catalytic residue H447 of hAChE. The per-residue free energy decomposition suggested that DPZ interacted with the residues in peripheral anionic site of hAChE, resulting in the greater binding affinity of DPZ than that of GLM toward hAChE. The binding free energy calculation based on MM-PBSA and MM-GBSA methods indicated that van der Waal interactions played a predominant role as the driving force for binding process of DPZ and GLM to hAChE. Moreover, the predicted total binding free energy of hAChE/DPZ was stronger than hAChE/GLM, which was consistent well with the experimental data. We hope that our findings provide useful information for further design of novel hAChE inhibitors. HIGHLIGHTS Anti-Alzheimer’s drugs donepezil and galantamine in complex with human acetylcholinesterase were explored by MD simulations and binding free energy calculations The MM-PB(GB)SA-based binding free energy indicated that donepezil exhibited a more favorable binding affinity to human acetylcholinesterase than galantamine The molecular rotation of galantamine during MD simulation resulted in the reduction of hydrogen bond occupancies with D74 and S203 The van der Waals interactions were considered as the major contributor to the binding of both drugs GRAPHICAL ABSTRACT

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Section: Binding Free Energy Calculationssupporting

confidence: 63%

Structural Dynamics and Susceptibility of Anti-Alzheimer’s Drugs Donepezil and Galantamine against Human Acetylcholinesterase

Nutho

Yanarojana²,

Supavilai³

2022

Trends Sci

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“…The indole alkaloids, mitragynine ( 39 ) and mitragynine oxidle B ( 40 ), have been identified as acetylcholinesterase (AChE) inhibitors by computational chemistry techniques. In the experiment on AChE inhibitory activity, the inhibitory effect of mitragynine on AChE was dose-dependent, and the IC 50 value was 3.57 μM (Innok et al 2021 ).…”

Section: Natural Products From Plants and Microorganisms With Neuropr...mentioning

confidence: 99%

Neurological disorders of COVID-19: insights to applications of natural products from plants and microorganisms

et al. 2022

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In addition to the typical respiratory manifestations, various disorders including involvement of the nerve system have been detected in COVID-19 ranging from 22 to 36%. Although growing records are focusing on neurological aspects of COVID-19, the pathophysiological mechanisms and related therapeutic methods remain obscure. Considering the increased concerns of SARS-CoV-2 potential for more serious neuroinvasion conditions, the present review attempts to focus on the neuroprotective effects of natural compounds as the principle source of therapeutics inhibiting multiple steps of the SARS-CoV-2 infection cycle. The great majority of the natural products with anti-SARS-CoV-2 activity mainly inhibit the attachment, entry and gene expression rather than the replication, assembly, or release. Although microbial-derived natural products comprise 38.5% of the known natural products with neuroprotective effects following viral infection, the neuroprotective potential of the majority of microorganisms is still undiscovered. Among natural products, chrysin, huperzine A, ginsenoside Rg1, pterostilbene, and terrein have shown potent in vitro neuroprotective activity and can be promising for new or repurpose drugs for neurological complications of SARS-CoV-2.

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Section: Potential Drug-drug Interactionsmentioning

confidence: 99%

“…Interactions of mitragynine with enzymes other than DMEs have also been reported. However, studies on these enzymes were very limited, with just acetylcholinesterase ( Innok et al, 2021 ) and cyclooxygenase ( Utar et al, 2011 ) being evaluated. Findings from these studies were less clinically relevant as the experiments were performed using enzymes from non-human sources i.e., electric eel for acetylcholinesterase, and rodent macrophage cell lines for cyclooxygenase, or the inhibition data showed mitragynine concentration that is hardly attained in human plasma, for example, IC 50 of 264 µM for acetylcholinesterase.…”

Section: Interactions With Enzymesmentioning

confidence: 99%

Kratom Alkaloids: Interactions With Enzymes, Receptors, and Cellular Barriers

et al. 2021

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Parallel to the growing use of kratom, there is a wealth of evidence from self-report, preclinical, and early clinical studies on therapeutic benefits of its alkaloids in particular for treating pain, managing substance use disorder, and coping with emotional or mental health conditions. On the other hand, there are also reports on potential health risks concerning kratom use. These two aspects are often discussed in reviews on kratom. Here, we aim to highlight specific areas that are of importance to give insights into the mechanistic of kratom alkaloids pharmacological actions. This includes their interactions with drug-metabolizing enzymes and predictions of clinical drug-drug interactions, receptor-binding properties, interactions with cellular barriers in regards to barrier permeability, involvement of membrane transporters, and alteration of barrier function when exposed to the alkaloids.

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In silico and in vitro anti-AChE activity investigations of constituents from Mytragyna speciosa for Alzheimer’s disease treatment

Cited by 11 publications

References 40 publications

Structural Dynamics and Susceptibility of Anti-Alzheimer’s Drugs Donepezil and Galantamine against Human Acetylcholinesterase

Structural Dynamics and Susceptibility of Anti-Alzheimer’s Drugs Donepezil and Galantamine against Human Acetylcholinesterase

Neurological disorders of COVID-19: insights to applications of natural products from plants and microorganisms

Kratom Alkaloids: Interactions With Enzymes, Receptors, and Cellular Barriers

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