Abstract | BACKGROUND: OBJECTIVE: our aim in this article was to investigate the inhibitory potential of five known compounds (2-6) with spiro skeleton against AChE and BChE using ELISA microplate assays. In addition to their ChE inhibitory effect, their physico-chemical properties were also calculated. Moreover, the present work aims at investigating the charge/geometrical effect of a hypothetical pharmacophore or bidentate site in a bioactive group, on the inhibition efficiency of spiro compounds 2-6 by using Petra/Osiris/ molinspiration (POM) and X-ray analyses. METHOD: In the present study, five compounds (2-6) with spiro skeleton have been synthesized and tested in vitro for their inhibitory potential against AChE and BChE using ELISA microtiter plate assays at 25 µg/mL. RESULTS: Results revealed that three of the spiro compounds tested exert more than 50% inhibition against one of cholinesterases. Compound 5 displayed 68.73 ± 4.73% of inhibition toward AChE, whereas compound 6 showed 56.17 ± 0.83% of inhibition toward BChE; these two previously synthesized compounds have been the most active hits. CONCLUSIONS: Our data obtained from screening of compounds 2-6 against the two cholinesterases indicate that three of these show good potential to selectively inhibit AChE or BChE. Spiro compounds 2, 5, and 6 exhibited the most potent activity of the series against AChE or BChE with inhibition values in the range 55-70%.
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Authors | Taibi Ben Hadda, Oualid Talhi, Artur S M Silva, Fatma Sezer Senol, Ilkay Erdogan Orhan, Abdur Rauf, Yahia N Mabkhot, Khaldoun Bachari, Ismail Warad, Thoraya A Farghaly, Ismail I Althagafi, Mohammad S Mubarak |
Journal | Mini reviews in medicinal chemistry
(Mini Rev Med Chem)
Vol. 18
Issue 8
Pg. 711-716
( 2018)
ISSN: 1875-5607 [Electronic] Netherlands |
PMID | 28714400
(Publication Type: Journal Article, Review)
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Copyright | Copyright© Bentham Science Publishers; For any queries, please email at [email protected]. |
Chemical References |
- Cholinesterase Inhibitors
- Spiro Compounds
- Acetylcholinesterase
- Butyrylcholinesterase
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Topics |
- Acetylcholinesterase
(chemistry, metabolism)
- Alzheimer Disease
(drug therapy)
- Butyrylcholinesterase
(chemistry, metabolism)
- Cholinesterase Inhibitors
(chemistry, metabolism, therapeutic use)
- Dose-Response Relationship, Drug
- Humans
- Models, Molecular
- Spiro Compounds
(chemistry, metabolism, therapeutic use)
- Structure-Activity Relationship
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