TY - JOUR
T1 - Synthesis of highly functionalised dispiropyrrolidine derivatives as novel acetylcholinesterase inhibitors
AU - We, Ang Chee
AU - Ali, Mohamed Ashraf
AU - Yoon, Yeong Keng
AU - Ismail, Rusli
AU - Choon, Tan Soo
AU - Khaw, Kooi Yeong
AU - Murugaiyah, Vikneswaran
AU - Lakshmipathi, Venu Sanjeevi
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2014/2
Y1 - 2014/2
N2 - In the effort of finding novel acetyl cholinesterase (AChE) inhibitors to improve the efficacy of Alzheimer's disease (AD) treatment, series of substituted aryl-1′-methyldispiro[indan-2,2′ pyrrolidine-3′, 2"-indan]-1,3,1′-trione and substituted 7′-aryl-5′, 6′,7′,7a′-tetrahydrodispiro-[indane-2,5′-pyrrolo[1,2-c] [1,3]thiazole-6′,2"-indan]-1,3,1"-trione analogues were synthesized using [3+2]-cycloaddition reactions. These newly synthesized pyrrolidine compounds were assayed for their biological activity using Ellman's method. The structural elucidation of the compounds was performed by using 1H-NMR, 13C-NMR, ESI-MS spectra and elemental analyses. Eight out of twenty synthesized compounds showed more than 50% inhibition at concentration of 10 μM. Compound 2e, 2i and 3e were among the most active one, giving IC50 value as 3.3 μM for 2e, 3.7 μM for 2i and 5.5 μM for 3e, respectively. Lineweaver-Burk plot indicated that 2i inhibits AChE in a competitive manner. Molecular modelling study was performed to disclose the binding interaction of these compounds with the active site of AChE.
AB - In the effort of finding novel acetyl cholinesterase (AChE) inhibitors to improve the efficacy of Alzheimer's disease (AD) treatment, series of substituted aryl-1′-methyldispiro[indan-2,2′ pyrrolidine-3′, 2"-indan]-1,3,1′-trione and substituted 7′-aryl-5′, 6′,7′,7a′-tetrahydrodispiro-[indane-2,5′-pyrrolo[1,2-c] [1,3]thiazole-6′,2"-indan]-1,3,1"-trione analogues were synthesized using [3+2]-cycloaddition reactions. These newly synthesized pyrrolidine compounds were assayed for their biological activity using Ellman's method. The structural elucidation of the compounds was performed by using 1H-NMR, 13C-NMR, ESI-MS spectra and elemental analyses. Eight out of twenty synthesized compounds showed more than 50% inhibition at concentration of 10 μM. Compound 2e, 2i and 3e were among the most active one, giving IC50 value as 3.3 μM for 2e, 3.7 μM for 2i and 5.5 μM for 3e, respectively. Lineweaver-Burk plot indicated that 2i inhibits AChE in a competitive manner. Molecular modelling study was performed to disclose the binding interaction of these compounds with the active site of AChE.
KW - Acetyl cholinesterase inhibitors
KW - Alzheimer's disease
KW - Cycloaddition
KW - Ellman's method
KW - Lineweaver-Burk plot
KW - Molecular modeling
KW - Pyrrolidine
UR - http://www.scopus.com/inward/record.url?scp=84893778062&partnerID=8YFLogxK
U2 - 10.2174/15701808113109990038
DO - 10.2174/15701808113109990038
M3 - Article
AN - SCOPUS:84893778062
VL - 11
SP - 156
EP - 161
JO - Letters in Drug Design and Discovery
JF - Letters in Drug Design and Discovery
SN - 1570-1808
IS - 2
ER -