NDLI: Kinetics and Molecular Docking Study of an Anti-diabetic Drug Glimepiride as Acetylcholinesterase Inhibitor: Implication for Alzheimer’s Disease-Diabetes Dual Therapy

Content Provider	Springer Nature Link
Author	Rizvi, Syed Mohd. Danish Shaikh, Sibhghatulla Naaz, Deeba Shakil, Shazi Ahmad, Adnan Haneef, Mohd. Abuzenadah, Adel M.
Copyright Year	2016
Abstract	At the present time, treatment of two most common degenerative disorders of elderly population i.e., Type 2 Diabetes Mellitus (T2DM) and Alzheimer’s disease (AD) is a major concern worldwide. As there are several evidences that proved strong linkages between these two disorders, the idea of using dual therapeutic agent for both the diseases might be considered as a good initiative. Earlier reports have revealed that oral anti-diabetic drugs such as peroxisome proliferator activated receptor γ (PPARγ) agonists (thiazolidinediones) when used in T2DM patients suffering from AD showed improved memory and cognition. However, the underlying mechanism still needs to be deciphered. Therefore, the present study was carried out to find whether glimepiride, an oral antidiabetic drug which is a PPARγ agonist could inhibit the activity of acetylcholine esterase (AChE) enzyme. Actually, AChE inhibitors seize the breakdown of acetylcholine which forms the main therapeutic strategy for AD. Here, glimepiride showed dose dependent inhibitory activity against AChE enzyme with IC$_{50}$ value of 235 μM. Kinetic analysis showed competitive inhibition, which was verified by in silico docking studies. Glimepiride was found to interact with AChE enzyme at the same locus as that of substrate acetylcholine iodide (AChI). Interestingly, amino acid residues, Q71, Y72, V73, D74, W86, N87, Y124, S125, W286, F295, F297, Y337, F338 and Y341 of AChE were found to be common for ‘glimepiride–AChE interaction’ as well as ‘AChI–AChE interaction’. Thus the present computational and kinetics study concludes that glimepiride and other thiazolidinediones derivatives could form the basis of future dual therapy against diabetes associated neurological disorders.
Starting Page	1475
Ending Page	1482
Page Count	8
File Format	PDF
ISSN	03643190
Journal	Neurochemical Research
Volume Number	41
Issue Number	6
e-ISSN	15736903
Language	English
Publisher	Springer US
Publisher Date	2016-02-17
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Alzheimer’s disease Acetylcholinesterase Acetylcholine iodide Competitive inhibition Glimepiride Type 2 Diabetes Mellitus Neurosciences Neurochemistry Biochemistry Cell Biology Neurology
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry Cellular and Molecular Neuroscience

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