Planta Med 2020; 86(15): 1118-1124
DOI: 10.1055/a-1199-7084
Biological and Pharmacological Activity
Original Papers

Isolation and Characterization of Acetylcholinesterase Inhibitors from Piper longum and Binding Mode Predictions[ # ]

Zakie Khatami
1   Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Science, Tehran, Iran
,
Sonja Herdlinger
2   Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Paracelsus Medical University, Salzburg, Austria
,
Parisa Sarkhail
3   Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Science, Tehran, Iran
,
Martin Zehl
4   Mass Spectrometry Centre & Department of Analytical Chemistry, University of Vienna, Vienna, Austria
,
Hanspeter Kaehlig
5   Institute of Organic Chemistry, University of Vienna, Vienna, Austria
,
Daniela Schuster
2   Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Paracelsus Medical University, Salzburg, Austria
,
1   Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Science, Tehran, Iran
› Author Affiliations
Supported by: Tehran University of Medical Sciences and Health Services 94-01-33-28734

Abstract

Restoration of cholinergic function is considered a rational approach to enhance cognitive performance. Acetylcholinesterase inhibitors are still the best therapeutic option for Alzheimerʼs disease. The fruits of Piper longum have been used in traditional medicines for the treatment of memory loss. It was demonstrated that the dichloromethane extract of these fruits is able to inhibit acetylcholinesterase. Thus, the aim of this study was to identify the contained acetylcholinesterase inhibitors. The active zones were presented via TLC-bioautography, and five compounds were isolated in the process of a bioassay-guided phytochemical investigation. Their structures were characterized as piperine, methyl piperate, guineenisine, pipercide, and pellitorine using spectroscopy and spectrometry methods (UV, IR, MS, 1H-, and 13C-NMR). In vitro acetylcholinesterase inhibitory activities of the isolates and their IC50 values were determined via a colorimetric assay. Three of them exhibited enzyme inhibitory activities, with piperine being the most potent compound (IC50 of 0.3 mM). In order to investigate the binding mode of the tested compounds, docking studies were performed using the X-ray crystal structure of acetylcholinesterase from Tetronarce californica with the Protein Data Bank code 1EVE. The content of the active compounds in the extract was determined by a developed HPLC method. Piperine was present in the maximum quantity in the fruits (0.57%), whereas methyl piperate contained the minimum content (0.10%).

# This article is dedicated to Prof. Wolfgang Kubelka for a lifetime of effort in the field of Pharmacognosy.


Supporting Information



Publication History

Received: 22 January 2020

Accepted after revision: 13 June 2020

Article published online:
15 July 2020

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