Construction of Spirooxindole Analogues Engrafted with Indole and Pyrazole Scaffolds as Acetylcholinesterase Inhibitors

Mohammad Shahidul Islam; Abdullah Mohammed Al-Majid; Mohammad Azam; Ved Prakash Verma; Assem Barakat; Matti Haukka; Abdullah A Elgazar; Amira Mira; Farid A Badria

doi:10.1021/acsomega.1c03978

Construction of Spirooxindole Analogues Engrafted with Indole and Pyrazole Scaffolds as Acetylcholinesterase Inhibitors

ACS Omega. 2021 Nov 12;6(47):31539-31556. doi: 10.1021/acsomega.1c03978. eCollection 2021 Nov 30.

Authors

Affiliations

¹ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
² Department of Chemistry, Banasthali Vidyapith, Banasthali 304022, Rajasthan, India.
³ Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, Alexandria 21321, Egypt.
⁴ Department of Chemistry, University of Jyväskylä, P.O. Box 35, FI-40014 Jyväskylä, Finland.
⁵ Department of Pharmacognosy, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh 33516, Egypt.
⁶ Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.

Abstract

Twenty-five new hits of spirooxindole analogs 8a-y engrafted with indole and pyrazole scaffolds were designed and constructed via a [3+2]cycloaddition (32CA) reaction starting from three components: new chalcone-based indole and pyrazole scaffolds 5a-d, substituted isatins 6a-c, and secondary amines 7a-d. The potency of the compounds were assessed in modulating cholinesterase (AChE) activity using Ellman's method. Compounds 8i and 8y showed the strongest acetylcholine esterase inhibition (AChEI) with IC₅₀ values of 24.1 and 27.8 μM, respectively. Molecular docking was used to study their interaction with the active site of hAChE.