neuro-primary-mental-health-2017-posters-abstracts

Page 62

allied

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International Conference on

NEUROLOGY AND NEUROSCIENCE

MENTAL HEALTH AND PRIMARY CARE

October 16-18, 2017 | Toronto, Canada

J Neurol Neurorehabil Res 2017 | Volume 2 Issue 3

hromen-4-ones has emerged as a ‘master key’ due

to its presence in wide range of activities related

to Alzheimer’s disease (AD), a multi-factorial cognitive

disorder. Polyfunctional compounds comprise a novel class

of therapeutic agents for the treatment of multi-factorial

disease like AD. In present study, total 33 chromen-4-ones

were designed and synthesized by making modifications at

different positions using Baker-Venkatraman rearrangement.

These compounds were primarily evaluated for in vitro

acetylcholinesterase (AChE) inhibitory, advanced glyacation

end products (AGEs) inhibition and antioxidant activity

and showed that most derivatives inhibited AChE with

IC50 values in the nanomolar range with additional AGEs

inhibitory and radical scavenging activities. The most active

compounds FLV-16, FLV-31 and FLV-32 (IC50=6.33, 6.48 and

5.83 nM, respectively) were also ameliorated scopolamine-

induced amnesia in mice model using moris water maze test

and also reversed the changes of various oxidative stress

markers (GSH and TBARS). The docking study revealed the

binding pattern of compounds simultaneously bind with

catalytic active site (CAS) and peripheral anionic site (PAS) of

AChE. Moreover, the in silico pharmacokinetic pro les were

predicted and revealed the drug-like properties with good

penetration in brain and good oral absorption of compounds.

After MD simulations, RMSD plots showed that the docked

complexes were quite stable for the specified time of 10 ns

with minor uctuations. Thus, newly designed chromen-

4-ones can act on different targets related to AD and the

poly-functional attribute of these compounds make them

potential candidates for the development of drugs for AD.

Polyfunctional chromen-4-ones based anti-Alzheimer’s agents: Design, synthesis and biological evaluation

Manjinder Singh

and

Om Silakari

Chitkara University, India

Punjabi University, India