Background: 2-Indolinone-based hydrazinecarbothioamides carrying a 3-phenylsulfonamide moiety (7–9) were designed by replacement of donepezil's pharmacophore group indanone with a 2-indolinone ring. Method: Compounds 7–9 were synthesized by reaction of N-(3-sulfamoylphenyl)hydrazinecarbothioamide (6) with 1H-indolin-2,3-diones (1–3). Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory effects of compounds 7–9 were assayed. Molecular modeling studies of 5-chloro-1,7-dimethyl-substituted compound 8e were carried out to determine the possible binding interactions at the active site of AChE. Results: Compound 8e showed the strongest inhibition against AChE (K_i = 0.52 ± 0.11 μM) as well as the highest selectivity (SI = 37.69). The selectivity for AChE over BuChE of compound 8e was approximately 17-times higher than donepezil and 26-times higher than galantamine. Conclusion: Further development of compounds 7–9 may present new promising agents for Alzheimer's treatment.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 13, No. 24

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Received 19 January 2021

Accepted 14 October 2021

Published online 10 November 2021

Published in print December 2021

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Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.future-science.com/doi/suppl/10.4155/fmc-2021-0018

Acknowledgments

The authors are grateful to Abdi İbrahim AŞ, who supplied donepezil.

Financial & competing interests disclosure

This work was supported by Istanbul University Scientific Research Projects (project no. TSA-2017-25638). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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