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Review
. 2022 Jul 12;12(31):19764-19855.
doi: 10.1039/d2ra03081k. eCollection 2022 Jul 6.

Inhibitory potential of nitrogen, oxygen and sulfur containing heterocyclic scaffolds against acetylcholinesterase and butyrylcholinesterase

Rami J Obaid  1 , Nafeesa Naeem  2 , Ehsan Ullah Mughal  2 , Munirah M Al-Rooqi  1 , Amina Sadiq  3 , Rabab S Jassas  4 , Ziad Moussa  5 , Saleh A Ahmed  1   6
Affiliations
Review

Inhibitory potential of nitrogen, oxygen and sulfur containing heterocyclic scaffolds against acetylcholinesterase and butyrylcholinesterase

Rami J Obaid et al. RSC Adv. .

Abstract

Heterocycles are the key structures in organic chemistry owing to their immense applications in the biological, chemical, and pharmaceutical fields. Heterocyclic compounds perform various noteworthy functions in nature, medication, innovation etc. Most frequently, pure nitrogen heterocycles or various positional combinations of nitrogen, oxygen, and sulfur atoms in five or six-membered rings can be found. Inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes is a popular strategy for the management of numerous mental diseases. In this context, cholinesterase inhibitors are utilized to relieve the symptoms of neurological illnesses like dementia and Alzheimer's disease (AD). The present review focuses on various heterocyclic scaffolds and their role in designing and developing new potential AChE and BChE inhibitors to treat AD. Moreover, a detailed structure-activity relationship (SAR) has been established for the future discovery of novel drugs for the treatment of AD. Most of the heterocyclic motifs have been used in the design of new potent cholinesterase inhibitors. In this regard, this review is an endeavor to summarize the biological and chemical studies over the past decade (2010-2022) describing the pursuit of new N, O and S containing heterocycles which can offer a rich supply of promising AChE and BChE inhibitory activities.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. Various heterocyclic scaffolds.
Fig. 2
Fig. 2. Selected examples of commercially available cholinesterase inhibitors.
Fig. 3
Fig. 3. Brain cholinergic signaling.
Fig. 4
Fig. 4. Diagrammatic representation of the active site of acetylcholinesterase.
Fig. 5
Fig. 5. Synthesis of acetylcholine.
Fig. 6
Fig. 6. Schematic representation of AD pathogenesis in light of the cholinergic and amyloid hypothesis.
Fig. 7
Fig. 7. Factors involved in AD progression.
Fig. 8
Fig. 8. Therapeutic strategies towards cognitive decline.
Fig. 9
Fig. 9. Synthesis, storage, discharge and termination of acetylcholine's action.
Fig. 10
Fig. 10. Mechanism of action of anti-AD drug.
Fig. 11
Fig. 11. SAR analysis of different pyrazole derivatives as AChE and BChE inhibitors.
Fig. 12
Fig. 12. SAR analysis of different imidazole derivatives as AChE and BChE inhibitors.
Fig. 13
Fig. 13. SAR analysis of different oxadiazole derivatives as AChE and BChE inhibitors.
Fig. 14
Fig. 14. SAR analysis of different pyrazoline derivatives as AChE and BChE inhibitors.
Fig. 15
Fig. 15. SAR analysis of different triazole derivatives as AChE and BChE inhibitors.
Fig. 16
Fig. 16. SAR analysis of different thiadiazole derivatives as AChE and BChE inhibitors.
Fig. 17
Fig. 17. SAR analysis of different pyrrolidine derivatives as AChE and BChE inhibitors.
Fig. 18
Fig. 18. SAR analysis of different piperidine derivatives as AChE and BChE inhibitors.
Fig. 19
Fig. 19. SAR analysis of different piperazine derivatives as AChE and BChE inhibitors.
Fig. 20
Fig. 20. SAR analysis of different quinoline derivatives as AChE and BChE inhibitors.
Fig. 21
Fig. 21. SAR analysis of different pyrimidine derivatives as AChE and BChE inhibitors.
Fig. 22
Fig. 22. SAR analysis of different triazine derivatives as AChE and BChE inhibitors.
Fig. 23
Fig. 23. SAR analysis of different pyridine derivatives as AChE and BChE inhibitors.
Fig. 24
Fig. 24. SAR analysis of different quinazolines derivatives as AChE and BChE inhibitors.
Fig. 25
Fig. 25. SAR analysis of different N, O and S based heterocycles as AChE and BChE inhibitors.
None
Ehsan Ullah Mughal
None
Saleh A. Ahmed
See this image and copyright information in PMC

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