| Title |
Kinetics and Molecular Docking Study of an Anti-diabetic Drug Glimepiride as Acetylcholinesterase Inhibitor: Implication for Alzheimer’s Disease-Diabetes Dual Therapy
|
|---|---|
| Published in |
Neurochemical Research, February 2016
|
| DOI | 10.1007/s11064-016-1859-3 |
| Pubmed ID | |
| Authors |
Syed Mohd. Danish Rizvi, Sibhghatulla Shaikh, Deeba Naaz, Shazi Shakil, Adnan Ahmad, Mohd. Haneef, Adel M. Abuzenadah |
| 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 IC50 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. |
Mendeley readers
The data shown below were compiled from readership statistics for 67 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 67 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 12 | 18% |
| Student > Ph. D. Student | 9 | 13% |
| Researcher | 9 | 13% |
| Student > Master | 5 | 7% |
| Professor | 3 | 4% |
| Other | 11 | 16% |
| Unknown | 18 | 27% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 12 | 18% |
| Pharmacology, Toxicology and Pharmaceutical Science | 9 | 13% |
| Chemistry | 6 | 9% |
| Psychology | 4 | 6% |
| Biochemistry, Genetics and Molecular Biology | 4 | 6% |
| Other | 9 | 13% |
| Unknown | 23 | 34% |
Attention Score in Context
This research output has an Altmetric Attention Score of 7. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 February 2016.
All research outputs
#4,184,175
of 22,849,304 outputs
Outputs from Neurochemical Research
#274
of 2,098 outputs
Outputs of similar age
#64,303
of 297,955 outputs
Outputs of similar age from Neurochemical Research
#9
of 41 outputs
Altmetric has tracked 22,849,304 research outputs across all sources so far. Compared to these this one has done well and is in the 80th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,098 research outputs from this source. They receive a mean Attention Score of 4.3. This one has done well, scoring higher than 82% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 297,955 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 77% of its contemporaries.
We're also able to compare this research output to 41 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 68% of its contemporaries.