Title:Synthesis, in silico Studies and Pharmacological Evaluation of a New
Series of Indanone Derivatives as Anti-Parkinsonian and Anti-Alzheimer’s
Agents
Volume: 19
Issue: 2
Author(s): Ranju Bansal*, Ranjit Singh and Pratibha Rana
Affiliation:
- University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India
Keywords:
Parkinson’s disease, Alzheimer’s disease, 2-benzylidene-1-indanone analogues, LPS, PPZ, IL-1β, TNF-α, MAO-B.
Abstract:
Objective: Parkinson’s disease (PD) and Alzheimer’s disease (AD) are the most common
forms of neurodegenerative disorders. The aim of the current work is to study the potential of
some new indanone derivatives for the treatment of these neurological disorders.
Methods: A new series of 4-(2-oxo-2-aminoethoxy)-2-benzylidene substituted indanone derivatives
have been synthesized and studied for anti-Parkinsonian and anti-Alzheimer’s effects. Substitution
of different aminoalkyl functionalities at the para position of 2-benzylidene moiety of
indanone ring resulted in the formation of potent anti-parkinsonian and anti-Alzheimer’s agents
(5-10). The neuroprotective effects of newly synthesized compounds were evaluated using
perphenazine (PPZ)-induced catatonia in rats and LPS-induced cognitive deficits in mice models.
Further, in silico molecular modelling studies of the new indanone derivatives were performed by
docking against the 3D structures of various neuroinflammatory mediators, such as interleukin-1β
(IL-1β), tumor necrosis factor-α (TNF-α) and monoamine oxidase-B (MAO-B), to gain the mechanistic
insights of their anti-Alzheimer’s and antiparkinsonian effects.
Results: The newly synthesized indanone analogues 5-10 were found effective against PPZinduced
motor dysfunction and LPS-induced memory impairment in animal models. Among
all the synthesized analogues, morpholine-substituted indanone 9 displayed maximum
anti-parkinsonian activity, even better than the standard drug L-DOPA, while pyrrolidine and
piperidine substituted analogues 5 and 6 were found to be the most potent anti-Alzheimer’s
agents.
Conclusion: The new 2-arylidene-1-indanone analogues show good potential as promising leads
for designing compounds against Parkinson’s and Alzheimer’s diseases.