Abstract
Alzheimer's disease (AD) is a progressive brain disorder which occurs due to lower levels of acetylcholine (ACh) neurotransmitters, and results in a gradual decline in memory and other cognitive processes. Acetycholinesterase (AChE) and butyrylcholinesterase (BChE) are considered to be primary regulators of the ACh levels in the brain. Evidence shows that AChE activity decreases in AD, while activity of BChE does not change or even elevate in advanced AD, which suggests a key involvement of BChE in ACh hydrolysis during AD symptoms. Therefore, inhibiting the activity of BChE may be an effective way to control AD associated disorders. In this regard, a series of quinoxaline derivatives 1-17 was synthesized and biologically evaluated against cholinesterases (AChE and BChE) and as well as against α- chymotrypsin and urease. The compounds 1-17 were found to be selective inhibitors for BChE, as no activity was found against other enzymes. Among the series, compounds 6 (IC50 = 7.7 ± 1.0 µM) and 7 (IC50 = 9.7 ± 0.9 µM) were found to be the most active inhibitors against BChE. Their IC50 values are comparable to the standard, galantamine (IC50 = 6.6 ± 0.38 µM). Their considerable BChE inhibitory activity makes them selective candidates for the development of BChE inhibitors. Structure-activity relationship (SAR) of this new class of selective BChE inhibitors has been discussed.
Keywords: Alzheimer's disease (AD), acetylcholine (ACh), quinoxaline, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), galantamine, urease, chymotrypsin.
Medicinal Chemistry
Title:Quinoxaline Derivatives: Novel and Selective Butyrylcholinesterase Inhibitors
Volume: 10 Issue: 7
Author(s): Aurang Zeb, Abdul Hameed, Latifullah Khan, Imran Khan, Kourosh Dalvandi, M. Iqbal Choudhary and Fatima Z. Basha
Affiliation:
Keywords: Alzheimer's disease (AD), acetylcholine (ACh), quinoxaline, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), galantamine, urease, chymotrypsin.
Abstract: Alzheimer's disease (AD) is a progressive brain disorder which occurs due to lower levels of acetylcholine (ACh) neurotransmitters, and results in a gradual decline in memory and other cognitive processes. Acetycholinesterase (AChE) and butyrylcholinesterase (BChE) are considered to be primary regulators of the ACh levels in the brain. Evidence shows that AChE activity decreases in AD, while activity of BChE does not change or even elevate in advanced AD, which suggests a key involvement of BChE in ACh hydrolysis during AD symptoms. Therefore, inhibiting the activity of BChE may be an effective way to control AD associated disorders. In this regard, a series of quinoxaline derivatives 1-17 was synthesized and biologically evaluated against cholinesterases (AChE and BChE) and as well as against α- chymotrypsin and urease. The compounds 1-17 were found to be selective inhibitors for BChE, as no activity was found against other enzymes. Among the series, compounds 6 (IC50 = 7.7 ± 1.0 µM) and 7 (IC50 = 9.7 ± 0.9 µM) were found to be the most active inhibitors against BChE. Their IC50 values are comparable to the standard, galantamine (IC50 = 6.6 ± 0.38 µM). Their considerable BChE inhibitory activity makes them selective candidates for the development of BChE inhibitors. Structure-activity relationship (SAR) of this new class of selective BChE inhibitors has been discussed.
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Zeb Aurang, Hameed Abdul, Khan Latifullah, Khan Imran, Dalvandi Kourosh, Choudhary Iqbal M. and Basha Z. Fatima, Quinoxaline Derivatives: Novel and Selective Butyrylcholinesterase Inhibitors, Medicinal Chemistry 2014; 10 (7) . https://dx.doi.org/10.2174/1573406410666140526145429
DOI https://dx.doi.org/10.2174/1573406410666140526145429 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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