TY - JOUR
T1 - Identification of novel acetylcholinesterase inhibitors
T2 - Indolopyrazoline derivatives and molecular docking studies
AU - Chigurupati, Sridevi
AU - Selvaraj, Manikandan
AU - Mani, Vasudevan
AU - Selvarajan, Kesavanarayanan Krishnan
AU - Mohammad, Jahidul Islam
AU - Kaveti, Balaji
AU - Bera, Hriday
AU - Palanimuthu, Vasanth Raj
AU - Teh, Lay Kek
AU - Salleh, Mohd Zaki
N1 - Funding Information:
The authors are thankful to AIMST University, Malaysia for providing the facilities for this project and the Ministry of Higher Education, Malaysia (MOHE) for funding the computational part (Software and Workstation) through the “TRGS” (grant no. 600-RMI/TRGS 5/3 (1/2014)-3 ).
Publisher Copyright:
© 2016 Elsevier Inc.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2016/8
Y1 - 2016/8
N2 - 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.
AB - 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.
KW - Acetylcholinesterase
KW - Antioxidant
KW - Indole
KW - Molecular docking
KW - Pyrazoline
UR - http://www.scopus.com/inward/record.url?scp=84988957420&partnerID=8YFLogxK
U2 - 10.1016/j.bioorg.2016.05.002
DO - 10.1016/j.bioorg.2016.05.002
M3 - Article
C2 - 27231830
AN - SCOPUS:84988957420
SN - 0045-2068
VL - 67
SP - 9
EP - 17
JO - Bioorganic Chemistry
JF - Bioorganic Chemistry
ER -