Identification of novel acetylcholinesterase inhibitors: Indolopyrazoline derivatives and molecular docking studies

Identification of novel acetylcholinesterase inhibitors: Indolopyrazoline derivatives and molecular docking studies

The synthesis of novel indolopyrazoline derivatives (P1-P4 and Q1-Q4) has been characterized and evaluated as potential anti-Alzheimer agents through in vitro Acetylcholinesterase (AChE) inhibition and radical scavenging activity (antioxidant) studies. Specifically, Q3 shows AChE inhibition (IC50: 0...

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Published in:Bioorganic Chemistry
Main Author: Chigurupati S.; Selvaraj M.; Mani V.; Selvarajan K.K.; Mohammad J.I.; Kaveti B.; Bera H.; Palanimuthu V.R.; Teh L.K.; Salleh M.Z.
Format: Article
Language:English
Published: Academic Press Inc. 2016
Online Access:https://www.scopus.com/inward/record.uri?eid=2-s2.0-84988957420&doi=10.1016%2fj.bioorg.2016.05.002&partnerID=40&md5=888f8a3acf498f30dda9c78f34d76321
id 2-s2.0-84988957420
spelling 2-s2.0-84988957420
Chigurupati S.; Selvaraj M.; Mani V.; Selvarajan K.K.; Mohammad J.I.; Kaveti B.; Bera H.; Palanimuthu V.R.; Teh L.K.; Salleh M.Z.
Identification of novel acetylcholinesterase inhibitors: Indolopyrazoline derivatives and molecular docking studies
2016
Bioorganic Chemistry
67

10.1016/j.bioorg.2016.05.002
https://www.scopus.com/inward/record.uri?eid=2-s2.0-84988957420&doi=10.1016%2fj.bioorg.2016.05.002&partnerID=40&md5=888f8a3acf498f30dda9c78f34d76321
The synthesis of novel indolopyrazoline derivatives (P1-P4 and Q1-Q4) has been characterized and evaluated as potential anti-Alzheimer agents through in vitro Acetylcholinesterase (AChE) inhibition and radical scavenging activity (antioxidant) studies. Specifically, Q3 shows AChE inhibition (IC50: 0.68 ± 0.13 μM) with strong DPPH and ABTS radical scavenging activity (IC50: 13.77 ± 0.25 μM and IC50: 12.59 ± 0.21 μM), respectively. While P3 exhibited as the second most potent compound with AChE inhibition (IC50: 0.74 ± 0.09 μM) and with DPPH and ABTS radical scavenging activity (IC50: 13.52 ± 0.62 μM and IC50: 13.13 ± 0.85 μM), respectively. Finally, molecular docking studies provided prospective evidence to identify key interactions between the active inhibitors and the AChE that furthermore led us to the identification of plausible binding mode of novel indolopyrazoline derivatives. Additionally, in-silico ADME prediction using QikProp shows that these derivatives fulfilled all the properties of CNS acting drugs. This study confirms the first time reporting of indolopyrazoline derivatives as potential anti-Alzheimer agents. © 2016 Elsevier Inc.
Academic Press Inc.
00452068
English
Article
author Chigurupati S.; Selvaraj M.; Mani V.; Selvarajan K.K.; Mohammad J.I.; Kaveti B.; Bera H.; Palanimuthu V.R.; Teh L.K.; Salleh M.Z.
spellingShingle Chigurupati S.; Selvaraj M.; Mani V.; Selvarajan K.K.; Mohammad J.I.; Kaveti B.; Bera H.; Palanimuthu V.R.; Teh L.K.; Salleh M.Z.
Identification of novel acetylcholinesterase inhibitors: Indolopyrazoline derivatives and molecular docking studies
author_facet Chigurupati S.; Selvaraj M.; Mani V.; Selvarajan K.K.; Mohammad J.I.; Kaveti B.; Bera H.; Palanimuthu V.R.; Teh L.K.; Salleh M.Z.
author_sort Chigurupati S.; Selvaraj M.; Mani V.; Selvarajan K.K.; Mohammad J.I.; Kaveti B.; Bera H.; Palanimuthu V.R.; Teh L.K.; Salleh M.Z.
title Identification of novel acetylcholinesterase inhibitors: Indolopyrazoline derivatives and molecular docking studies
title_short Identification of novel acetylcholinesterase inhibitors: Indolopyrazoline derivatives and molecular docking studies
title_full Identification of novel acetylcholinesterase inhibitors: Indolopyrazoline derivatives and molecular docking studies
title_fullStr Identification of novel acetylcholinesterase inhibitors: Indolopyrazoline derivatives and molecular docking studies
title_full_unstemmed Identification of novel acetylcholinesterase inhibitors: Indolopyrazoline derivatives and molecular docking studies
title_sort Identification of novel acetylcholinesterase inhibitors: Indolopyrazoline derivatives and molecular docking studies
publishDate 2016
container_title Bioorganic Chemistry
container_volume 67
container_issue
doi_str_mv 10.1016/j.bioorg.2016.05.002
url https://www.scopus.com/inward/record.uri?eid=2-s2.0-84988957420&doi=10.1016%2fj.bioorg.2016.05.002&partnerID=40&md5=888f8a3acf498f30dda9c78f34d76321
description The synthesis of novel indolopyrazoline derivatives (P1-P4 and Q1-Q4) has been characterized and evaluated as potential anti-Alzheimer agents through in vitro Acetylcholinesterase (AChE) inhibition and radical scavenging activity (antioxidant) studies. Specifically, Q3 shows AChE inhibition (IC50: 0.68 ± 0.13 μM) with strong DPPH and ABTS radical scavenging activity (IC50: 13.77 ± 0.25 μM and IC50: 12.59 ± 0.21 μM), respectively. While P3 exhibited as the second most potent compound with AChE inhibition (IC50: 0.74 ± 0.09 μM) and with DPPH and ABTS radical scavenging activity (IC50: 13.52 ± 0.62 μM and IC50: 13.13 ± 0.85 μM), respectively. Finally, molecular docking studies provided prospective evidence to identify key interactions between the active inhibitors and the AChE that furthermore led us to the identification of plausible binding mode of novel indolopyrazoline derivatives. Additionally, in-silico ADME prediction using QikProp shows that these derivatives fulfilled all the properties of CNS acting drugs. This study confirms the first time reporting of indolopyrazoline derivatives as potential anti-Alzheimer agents. © 2016 Elsevier Inc.
publisher Academic Press Inc.
issn 00452068
language English
format Article
accesstype
record_format scopus
collection Scopus
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