Metformin and Its Sulfenamide Prodrugs Inhibit Human Cholinesterase Activity
Joint Authors
Sikora, Joanna
Mikiciuk-Olasik, Elżbieta
Markowicz-Piasecka, Magdalena
Mateusiak, Łukasz
Huttunen, Kristiina M.
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-07-09
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
The results of epidemiological and pathophysiological studies suggest that type 2 diabetes mellitus (T2DM) may predispose to Alzheimer’s disease (AD).
The two conditions present similar glucose levels, insulin resistance, and biochemical etiologies such as inflammation and oxidative stress.
The diabetic state also contributes to increased acetylcholinesterase (AChE) activity, which is one of the factors leading to neurodegeneration in AD.
The aim of this study was to assess in vitro the effects of metformin, phenformin, and metformin sulfenamide prodrugs on the activity of human AChE and butyrylcholinesterase (BuChE) and establish the type of inhibition.
Metformin inhibited 50% of the AChE activity at micromolar concentrations (2.35 μmol/mL, mixed type of inhibition) and seemed to be selective towards AChE since it presented low anti-BuChE activity.
The tested metformin prodrugs inhibited cholinesterases (ChE) at nanomolar range and thus were more active than metformin or phenformin.
The cyclohexyl sulfenamide prodrug demonstrated the highest activity towards both AChE (IC50 = 890 nmol/mL, noncompetitive inhibition) and BuChE (IC50 = 28 nmol/mL, mixed type inhibition), while the octyl sulfenamide prodrug did not present anti-AChE activity, but exhibited mixed inhibition towards BuChE (IC50 = 184 nmol/mL).
Therefore, these two bulkier prodrugs were concluded to be the most selective compounds for BuChE over AChE.
In conclusion, it was demonstrated that biguanides present a novel class of inhibitors for AChE and BuChE and encourages further studies of these compounds for developing both selective and nonselective inhibitors of ChEs in the future.
American Psychological Association (APA)
Markowicz-Piasecka, Magdalena& Sikora, Joanna& Mateusiak, Łukasz& Mikiciuk-Olasik, Elżbieta& Huttunen, Kristiina M.. 2017. Metformin and Its Sulfenamide Prodrugs Inhibit Human Cholinesterase Activity. Oxidative Medicine and Cellular Longevity،Vol. 2017, no. 2017, pp.1-11.
https://search.emarefa.net/detail/BIM-1195579
Modern Language Association (MLA)
Markowicz-Piasecka, Magdalena…[et al.]. Metformin and Its Sulfenamide Prodrugs Inhibit Human Cholinesterase Activity. Oxidative Medicine and Cellular Longevity No. 2017 (2017), pp.1-11.
https://search.emarefa.net/detail/BIM-1195579
American Medical Association (AMA)
Markowicz-Piasecka, Magdalena& Sikora, Joanna& Mateusiak, Łukasz& Mikiciuk-Olasik, Elżbieta& Huttunen, Kristiina M.. Metformin and Its Sulfenamide Prodrugs Inhibit Human Cholinesterase Activity. Oxidative Medicine and Cellular Longevity. 2017. Vol. 2017, no. 2017, pp.1-11.
https://search.emarefa.net/detail/BIM-1195579
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1195579