alexa Synthesis, Biological Evaluation and Molecular Modeling
ISSN: 2161-0444

Medicinal Chemistry
Open Access

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Research Article

Synthesis, Biological Evaluation and Molecular Modeling of (E)- 3-Propargylene-1, 3-Dihydro-2H-Indol-2-Ones as Acetyl- and Butyrylcholinesterase Inhibitors for the Treatment of Alzheimer's Disease

Ying Dong1#, Xiao Ming Zha2#, Xue Ping Chu1#, Di Kang2#, Su Lan Luo1#, Tao Lu1* and Qing Fa Zhou1*

1Department of Organic Chemistry, College of Science, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, PR China

2Jiangsu Center for Drug Screening, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, PR China

#These authors contributed equally to this work

*Corresponding Authors:
Tao Lu
Department of Organic Chemistry
College of Science
China Pharmaceutical University
24 Tongjiaxiang, Nanjing
210009, PR China
E-mail: [email protected]
 
Qing Fa Zhou
Department of Organic Chemistry
College of Science
China Pharmaceutical University
24 Tongjiaxiang, Nanjing
210009, PR China
Tel: +0086 025 86185172
E-mail: [email protected]

Received date: May 16, 2016; Accepted date: May 27, 2016; Published date: June 02, 2016

Citation: Dong Y, Zha XM, Chu XP, Kang D, Luo SL, et al. (2016) Synthesis, Biological Evaluation and Molecular Modeling of (E)-3-Propargylene-1, 3-Dihydro-2H-Indol-2-Ones as Acetyl- and Butyrylcholinesterase Inhibitors for the Treatment of Alzheimer's Disease. Med chem (Los Angeles) 6:372-376. doi:10.4172/2161-0444.1000372

Copyright: © 2016 Dong Y, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

 

Abstract

The synthesis, pharmacological evaluation and molecular modeling of (E)-3-propargylene-1,3-dihydro-2Hindol- 2-ones, targeting both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), are described. In vitro inhibition experiments of AChE and BuChE showed that compound 2, 5 and 12 are able to inhibit the two forms of cholinesterases in the submicromolar range. The most selective inhibitor of EeAChE (acetylcholinesterase, E.C. 3.1.1.7, from Electrophorus electricus) and eqBuChE (butylcholinesterase, E.C. 3.1.1.8, from equine serum) in this series are compound 9 (IC50=0.011 ± 0.018 μM) and compound 14 (IC50=0.12 ± 0.22 μM) respectively. But the substitution at 5- or 6- position of indolones is not generally favored for eqBuChE inhibition. Kinetic studies of the BuChE inhibition suggested that compound 1 and 5 produce a mixed inhibition pattern. The molecular modeling investigation confirmed the result and indicated that π-π stacking interaction is a main contributor to the increase of inhibition efficiency.

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