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

• 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
• ISSN: 00452068
• DOI: 10.1016/j.bioorg.2016.05.002

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.