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Derivatives of diisopropyl phenoxyphosphate with controlled reactivity for enhancement of Acetylcholine (ACh) neurotransmitter
Sheikh HK, Arshad T, Mohammad ZS, Moussa IK, Usman R, Hasan MM.. Pakistan journal of pharmaceutical sciences, 2020-09-01
Topic: Brain proteins, microglia and lab models
Here, new phenoxide derivatives of diisopropyl flourophosphate for reaction with Lewis basic sites on acetyl cholinesterase (AChE) were designed. Such binding interaction or reaction inhibits the hydrolysis of the acetylcholine (ACh) neurotransmitter thus enhancing its concentration. This increased neurotransmitter concentration can enhance memory and cognition thus improving symptoms of neurodegenerative diseases such as Alzheimer disease and down syndrome. For docking analysis, we particularly targeted those reception sites on AChE that interacts with the ACh. This led to structural design of derivatives of diisopropyl phenoxyphosphate with controlled reactivity stemming from para substituted phenoxide leaving group. Impact of electron donating (CH 3 , OCH 3 ) and withdrawing substituents (COCH 3 ) on para position of phenol group on rate of acyl addition elimination reaction was modeled using QM DFT technique. Difference in activation energy between electron donating and withdrawing substituents on phenoxide was noted hence making the derivatives of diisopropyl phenoxyphosphate less reactive and more selective. Docking also confirmed binding of designed derivatives with AChE. Hence novel derivatives with high binding energy and controlled reactivity were designed for retrosynthesis.
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APA 7th
Sheikh, H. K., Arshad, T., Mohammad, Z. S., Moussa, I. K., Usman, R., & Hasan, M. M. (2020). Derivatives of diisopropyl phenoxyphosphate with controlled reactivity for enhancement of Acetylcholine (ACh) neurotransmitter. Pakistan journal of pharmaceutical sciences.
Vancouver
Sheikh HK, Arshad T, Mohammad ZS, Moussa IK, Usman R, Hasan MM. Derivatives of diisopropyl phenoxyphosphate with controlled reactivity for enhancement of Acetylcholine (ACh) neurotransmitter. Pakistan journal of pharmaceutical sciences. 2020. PMID: 33832896.
BibTeX
@article{sheikh2020-33832896,
author = {Sheikh, H. K. and Arshad, T. and Mohammad, Z. S. and Moussa, I. K. and Usman, R. and Hasan, M. M.},
title = {{Derivatives of diisopropyl phenoxyphosphate with controlled reactivity for enhancement of Acetylcholine (ACh) neurotransmitter}},
journal = {Pakistan journal of pharmaceutical sciences},
year = {2020},
pmid = {33832896}
}
Built from the record alzhub holds for this paper, not looked up. This record has no DOI, so the citation leaves it out. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
Key findings
- This led to structural design of derivatives of diisopropyl phenoxyphosphate with controlled reactivity stemming from para substituted phenoxide leaving group.
- Impact of electron donating (CH 3 , OCH 3 ) and withdrawing substituents (COCH 3 ) on para position of phenol group on rate of acyl addition elimination reaction was modeled using QM DFT technique.
- Difference in activation energy between electron donating and withdrawing substituents on phenoxide was noted hence making the derivatives of diisopropyl phenoxyphosphate less reactive and more selective.
- Docking also confirmed binding of designed derivatives with AChE.
- Hence novel derivatives with high binding energy and controlled reactivity were designed for retrosynthesis.
Why it matters
This work designed and modeled new chemical derivatives intended to inhibit acetylcholinesterase and raise acetylcholine levels. It is computational and docking work only, with no testing in animals or people, so it does not establish any treatment, cure or prevention for Alzheimer's disease.
Study details
- Evidence strengthLow
How this study scored 25/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, so that was left out: it earned 24 of the 96 points we could judge it on, which is 25 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Pakistan journal of pharmaceutical sciences) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 0 / 6 | Cited 0.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Muhammad Mohtasheemul Hasan: h-index 16 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | University of Karachi: institution h-index 209 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33832896) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 24 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 24 of the 96 points we could judge it on is 25 out of 100. |
| Total | 25 / 100 | — |
What each of these 20 components measures, and what this score is not →
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