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

Autor:	Thanyada Rungrotmongkol, Netnapa Chana, Asadhawut Hiranrat, Wansiri Innok, Panita Kongsune
Rok vydání:	2021
Předmět:	Protein Conformation Drug Evaluation Preclinical Molecular Dynamics Simulation 01 natural sciences Magnoliopsida chemistry.chemical_compound Alzheimer Disease 0103 physical sciences Drug Discovery Humans Computer Simulation heterocyclic compounds Oxindole Physical and Theoretical Chemistry Flavonoids Indole test chemistry.chemical_classification Binding Sites 010304 chemical physics Plant Extracts Alkaloid Biological activity Acetylcholinesterase Acetylcholine 0104 chemical sciences Computer Science Applications Molecular Docking Simulation Plant Leaves 010404 medicinal & biomolecular chemistry Neuroprotective Agents Enzyme chemistry Biochemistry Docking (molecular) Mitragynine Cholinesterase Inhibitors Protein Binding
Zdroj:	Journal of Computer-Aided Molecular Design. 35:325-336
ISSN:	1573-4951 0920-654X
DOI:	10.1007/s10822-020-00372-4
Popis:	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.
Databáze:	OpenAIRE
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