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Abstract #24626 Published in IGR 11-4
Evaluation of a new lead for acetylcholinesterase inhibition
Khorana N; Markmee S; Ingkaninan K; Ruchirawat S; Kitbunnadaj R; Pullagurla MRMedicinal Chemistry Research 2009; 18: 231-241
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 (IC(50) = 7.0 (plus or minus) 1.4 (mu)M) and compound 4 (IC(50) = 5.5 (plus or minus) 1.0 (mu)M) displayed potent AChE inhibition. These compounds are currently the lead compounds for further studies in our laboratory.
N. Khorana. Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok 65000, Thailand. nantaka@hotmail.com
Classification:
11.2 Cholinergic drugs (Part of: 11 Medical treatment)
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
