Evaluation of a new lead for acetylcholinesterase inhibition

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• 作者：Nantaka Khorana (1)
  Sutthatip Markmee (1)
  Kornkanok Ingkaninan (1)
  Somsak Ruchirawat (2)
  Ruengwit Kitbunnadaj (1)
  Manik Reddy Pullagurla (3)
  
• 关键词：Acetylcholinesterase inhibitor ; Butyrylcholinesterase inhibitor ; Isoquinoline analogs ; Synthesis
• 刊名：Medicinal Chemistry Research
• 出版年：2009
• 出版时间：March 2009
• 年：2009
• 卷：18
• 期：3
• 页码：231-241
• 全文大小：452KB
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• 作者单位：Nantaka Khorana (1)
  Sutthatip Markmee (1)
  Kornkanok Ingkaninan (1)
  Somsak Ruchirawat (2)
  Ruengwit Kitbunnadaj (1)
  Manik Reddy Pullagurla (3)
  
  1. Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, 65000, Thailand
  2. Chulabhorn Research Institute, Bangkok, 10210, Thailand
  3. Biophore Pharmaceuticals Pvt. Ltd, Kukatpally, Hyderabad, 500072, India
  

文摘

Acetylcholine is the most common neurotransmitter of the parasympathetic nervous system. Several cholinergic drugs are widely used in Alzheimer’s disease, urinary retention, glaucoma, and myasthenia gravis. Acetylcholinesterase is the enzyme which destroys naturally occurring acetylcholine, and acetylcholinesterase inhibitors (AChEIs) which block the enzyme are currently used in the treatment of several diseases, most importantly Alzheimer’s disease. Previous studies from our laboratory have shown a few isoquinoline analogs to be potential acetylcholinesterase inhibitors. In the present study we have extended analysis of the structure–activity relationship (SAR) of the isoquinoline ring system as an AChEI. The corresponding reduced form of 1-(3,4-dimethoxybenzyl)-6,7-dimethoxyisoquinoline, ring-opened analog, and related analogs were evaluated for AChE inhibitory activity. Our results showed that the dihydroisoquinoline ring analog compound 6 (IC50?=?7.0?±?1.4?μM) and compound 4 (IC50?=?5.5?±?1.0?μM) displayed potent AChE inhibition. These compounds are currently the lead compounds for further studies in our laboratory.