Isolation, in Vitro Evaluation and Molecular Docking of Acetylcholinesterase Inhibitors From South African Amaryllidaceae

Isolation, in Vitro Evaluation and Molecular Docking of Acetylcholinesterase Inhibitors From South African Amaryllidaceae Publisher Pubmed

Sibanyoni MN¹ ; Chaudhary SK¹ ; Chen W¹ ; Adhami HR² ; Combrinck S^{1, 3} ; Maharaj V⁴ ; Schuster D⁵ ; Viljoen A^{2, 3}

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1. Department of Pharmaceutical Sciences, Faculty of Science, Tshwane University of Technology, Pretoria, South Africa
2. Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
3. SAMRC Herbal Drugs Research Unit, Faculty of Science, Tshwane University of Technology, Pretoria, South Africa
4. Department of Chemistry, Faculty of Natural and Agricultural Sciences, University of Pretoria, Pretoria, South Africa
5. Institute of Pharmacy, Department of Pharmaceutical and Medicinal Chemistry, Paracelsus Medical University of Salzburg, Salzburg, Austria

Source: Fitoterapia Published:2020

Abstract

Inhibition of acetylcholinesterase (AChE) is considered a promising strategy for the treatment of Alzheimer's disease (AD) and dementia. Members of the Amaryllidaceae family are well known for their pharmacologically active alkaloids, including galanthamine, which is used to treat AD. The aim of this study was to evaluate the potential of South African Amaryllidaceae species to inhibit AChE, to isolate the active compounds, and probe their ability to bind the enzyme using molecular docking. The AChE inhibitory activity of extracts of 41 samples, representing 14 genera and 28 species, as well as isolated compounds, were evaluated in vitro using a qualitative thin layer chromatography (TLC) bio-autography assay and Ellman's method in a quantitative 96-well microplate assay. Targeted isolation of compounds was achieved with the aid of preparative-high perfomance liquid chromatography-mass spectrometry. The structures of the isolates were elucidated using nuclear magnetic resonance spectrocopy, and were docked into the active site of AChE to rationalise their biological activities. The most active species were found to be Amaryllis belladonna L (IC50 14.3 ± 2.6 μg/mL), Nerine huttoniae Schonland (IC50 45.3 ± 0.4 μg/mL) and Nerine undulata (L.) Herb. (IC50 52.8 ± 0.5 μg/mL), while TLC bio-autography indicated the presence of several active compounds in the methanol extracts. Four compounds, isolated from A. belladonna, were identified as belladine, undulatine, buphanidrine and acetylcaranine. Acetylcaranine and undulatine were previously isolated from A. belladonna, while belladine and buphanidrine were reported from other South African Amaryllidaceae species. Using Ellman's method, acetylcaranine was found to be the most active of the isolates towards AChE, with an IC50 of 11.7 ± 0.7 μM, comparable to that of galanthamine (IC50 = 6.19 ± 2.60 μM). Molecular docking successfully predicted the binding modes of ligands within receptor binding sites. Acetylcaranine was predicted by the docking workflow to have the highest activity, which corresponds to the in vitro results. Both qualitative and quantitative assays indicate that several South African Amaryllidaceae species are notable AChE inhibitors. © 2020 Elsevier B.V.

2. Introduction of Marine-Derived Streptomyces Sp. Utmc 1334 As a Source of Pyrrole Derivatives With Anti-Acetylcholinesterase Activity, Journal of Applied Microbiology (2018)

3. Anti-Cholinesterase and Neuroprotective Activities of Sweet and Bitter Apricot Kernels (Prunus Armeniaca L.), Iranian Journal of Pharmaceutical Research (2020)

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Mina Saeedi (1)

Hamid Reza Adhami (1)

Style	Citing Format
MLA	Sibanyoni MN, et al.. "Isolation, in Vitro Evaluation and Molecular Docking of Acetylcholinesterase Inhibitors From South African Amaryllidaceae." Fitoterapia, vol. 146, no. , 2020, pp. -.
APA	Sibanyoni MN, Chaudhary SK, Chen W, Adhami HR, Combrinck S, Maharaj V, Schuster D, Viljoen A (2020). Isolation, in Vitro Evaluation and Molecular Docking of Acetylcholinesterase Inhibitors From South African Amaryllidaceae. Fitoterapia, 146(), -.
Chicago	Sibanyoni MN, Chaudhary SK, Chen W, Adhami HR, Combrinck S, Maharaj V, Schuster D, Viljoen A. "Isolation, in Vitro Evaluation and Molecular Docking of Acetylcholinesterase Inhibitors From South African Amaryllidaceae." Fitoterapia 146, no. (2020): -.
Harvard	Sibanyoni MN et al. (2020) 'Isolation, in Vitro Evaluation and Molecular Docking of Acetylcholinesterase Inhibitors From South African Amaryllidaceae', Fitoterapia, 146(), pp. -.
Vancouver	Sibanyoni MN, Chaudhary SK, Chen W, Adhami HR, Combrinck S, Maharaj V, et al.. Isolation, in Vitro Evaluation and Molecular Docking of Acetylcholinesterase Inhibitors From South African Amaryllidaceae. Fitoterapia. 2020;146():-.
BibTex	@article{ author = {Sibanyoni MN and Chaudhary SK and Chen W and Adhami HR and Combrinck S and Maharaj V and Schuster D and Viljoen A}, title = {Isolation, in Vitro Evaluation and Molecular Docking of Acetylcholinesterase Inhibitors From South African Amaryllidaceae}, journal = {Fitoterapia}, volume = {146}, number = {}, pages = {-}, year = {2020} }
RIS	TY - JOUR AU - Sibanyoni MN AU - Chaudhary SK AU - Chen W AU - Adhami HR AU - Combrinck S AU - Maharaj V AU - Schuster D AU - Viljoen A TI - Isolation, in Vitro Evaluation and Molecular Docking of Acetylcholinesterase Inhibitors From South African Amaryllidaceae JO - Fitoterapia VL - 146 IS - SP - EP - PY - 2020 ER -

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