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

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Abstract

Acetylcholinesterase (AChE), one of the major therapeutic strategies for the treatment of Alzheimer's disease (AD) is to increase the acetylcholine (ACh) level in the brain by inhibiting the biological activity of AChE. In this present work, a set of alkaloids and flavonoids against AChE enzyme were screened by computational chemistry techniques. The docking results showed that among alkaloid compounds the oxindole alkaloid namely mitragynine oxidole B (MITOB) and the indole alkaloids namely mitragynine (MIT) exhibited a good binding affinity towards AChE. These two compounds were then studied by molecular dynamics (MD) simulations. The binding free energy calculation and ligand–protein binding pattern suggested that both alkaloids could interact with AChE very well. Since MIT is the main alkaloid constituent of Mytragyna speciose leaves, this compound was isolated from M. speciose leaves and tested for anti-AChE activity. As a result, the isolated MIT had an inhibitory activity with pIC50 value of 3.57. This finding provided that the mitragynine compound has the potential to be as a therapeutic agent for further anti-AChE drug development in treatment of Alzheimer’s disease.

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Acknowledgements

This work was financially supported by the Thaksin University Research Fund and the Graduate School of Thaksin University. The authors would like to thank the Computational Chemistry Unit Cell, Faculty of Science, Chulalongkorn University, and the Department of Chemistry, Faculty of Science, Thaksin University, for providing research facilities, software packages and computing times.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, Thaksin University, Phattalung, 93210, Thailand

    Wansiri Innok, Asadhawut Hiranrat, Netnapa Chana & Panita Kongsune

  2. Biocatalyst and Environmental Biotechnology Research Unit, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand

    Thanyada Rungrotmongkol

  3. Program in Bioinformatics and Computational Biology, Graduate School, Chulalongkorn University, Bangkok, 10330, Thailand

    Thanyada Rungrotmongkol

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  1. Wansiri Innok
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Innok, W., Hiranrat, A., Chana, N. et al. In silico and in vitro anti-AChE activity investigations of constituents from Mytragyna speciosa for Alzheimer’s disease treatment. J Comput Aided Mol Des 35, 325–336 (2021). https://doi.org/10.1007/s10822-020-00372-4

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