Synthesis of a New Class of Spirooxindole-Benzo[b]Thiophene-Based Molecules as Acetylcholinesterase Inhibitors

被引：24

作者：

Barakat, Assem ^{[1
,2
]}

Alshahrani, Saeed ^{[1
]}

Al-Majid, Abdullah Mohammed ^{[1
]}

Ali, M. ^{[1
]}

Altowyan, Mezna Saleh ^{[3
]}

Islam, Mohammad Shahidul ^{[1
]}

Alamary, Abdullah Saleh ^{[1
]}

Ashraf, Sajda ^{[4
]}

Ul-Haq, Zaheer ^{[4
]}

机构：

[1] King Saud Univ, Coll Sci, Dept Chem, POB 2455, Riyadh 11451, Saudi Arabia

[2] Alexandria Univ, Fac Sci, Dept Chem, POB 426, Alexandria 21321, Egypt

[3] Princess Nourah Bint Abdulrahman Univ, Coll Sci, Dept Chem, Riyadh 11564, Saudi Arabia

[4] Univ Karachi, Dr Panjwani Ctr Mol Med & Drug Res, Int Ctr Chem & Biol Sci, Karachi 75270, Pakistan

来源：

MOLECULES | 2020年 / 25卷 / 20期

关键词：

spirooxindole; benzo[b]thiophene; acetylcholinesterase inhibitory activity; molecular docking; SPIROOXINDOLE; BENZOTHIOPHENE; DERIVATIVES; DISCOVERY; DRUG;

D O I：

10.3390/molecules25204671

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 mu M center dot 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 pi-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.

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页数：16

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