Metformin and Its Sulfenamide Prodrugs Inhibit Human Cholinesterase Activity

المؤلفون المشاركون

Sikora, Joanna
Mikiciuk-Olasik, Elżbieta
Markowicz-Piasecka, Magdalena
Mateusiak, Łukasz
Huttunen, Kristiina M.

المصدر

Oxidative Medicine and Cellular Longevity

العدد

المجلد 2017، العدد 2017 (31 ديسمبر/كانون الأول 2017)، ص ص. 1-11، 11ص.

الناشر

Hindawi Publishing Corporation

تاريخ النشر

2017-07-09

دولة النشر

مصر

عدد الصفحات

11

التخصصات الرئيسية

الأحياء

الملخص 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.

نمط استشهاد جمعية علماء النفس الأمريكية (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

نمط استشهاد الجمعية الأمريكية للغات الحديثة (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

نمط استشهاد الجمعية الطبية الأمريكية (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

نوع البيانات

مقالات

لغة النص

الإنجليزية

الملاحظات

Includes bibliographical references

رقم السجل

BIM-1195579