Synthesis of a New Class of Spirooxindole–Benzo[<i>b</i>]Thiophene-Based Molecules as Acetylcholinesterase Inhibitors
Assem Barakat,
Saeed Alshahrani,
Abdullah Mohammed Al-Majid,
M. Ali,
Mezna Saleh Altowyan,
Mohammad Shahidul Islam,
Abdullah Saleh Alamary,
Sajda Ashraf,
Zaheer Ul-Haq
Affiliations
Assem Barakat
Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
Saeed Alshahrani
Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
Abdullah Mohammed Al-Majid
Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
M. Ali
Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
Mezna Saleh Altowyan
Department of Chemistry, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh 11564, Saudi Arabia
Mohammad Shahidul Islam
Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
Abdullah Saleh Alamary
Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
Sajda Ashraf
Dr. Panjwani Center for Molecular medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
Zaheer Ul-Haq
Dr. Panjwani Center for Molecular medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
A series of new oxindole-based spiro-heterocycles bearing the benzo[b]thiophene motif were synthesized via a 1,3-dipolar cycloaddition reaction and their acetylcholinesterase (AChE) inhibitory activity was evaluated. All the synthesized compounds exhibited moderate inhibitory activities against AChE, while IIc was found to be the most active analog with an IC50 value of 20,840 µM·L−1. Its molecular structure was a 5-chloro-substituted oxindole bearing benzo[b]thiophene and octahydroindole moieties. Based on molecular docking studies, IIc was strongly bound to the catalytic and peripheral anionic sites of the protein through hydrophilic, hydrophobic, and π-stacking interactions with Asp74, Trp86, Tyr124, Ser125, Glu202, Ser203, Trp236, Trp286, Phe297, Tyr337, and Tyr341. These interactions also indicated that the multiplicity of the IIc aromatic core significantly favored its activity.
