20 / 27
Page 76
allied
academies
J Pharmacol Ther Res 2017 Volume 1 Issue 2
November 02-03, 2017 Chicago, USA
4
th
International Congress on
International Conference and Exhibition on
Drug Discovery, Designing and Development
Biochemistry, Molecular Biology: R&D
&
A
lzheimer’s disease (AD), a complex neurodegenerative
brain disorder, a most common cause of dementia
among elderly people. To date, the AD is being managed
by maintaining the levels of acetylcholine by inhibiting
acetylcholinesterase (AChE). Polyfunctional compounds
comprise a novel class of therapeutic agents for the treatment
of multi-factorial disease like AD. Following this approach
integrated with polyfunctional nature of flavonoids, a novel
flavonoid based compounds were designed, synthesized
and biologically evaluated against AChE, advanced glycation
end products (AGEs) formation with additional free radical
scavenging activity. The
in vitro
studies showed that the
majority of synthesized derivatives inhibited AChE with
IC
50
values in the nanomolar range along with good AGEs
inhibitory and radical scavenging activity. Among them, 7m,
strongly inhibited AChE and was found to be more potent
than the reference compound donepezil. Its potent inhibitory
activity has been justified by docking analysis that revealed
its dual binding simultaneously to catalytic active site (CAS)
and peripheral anionic site (PAS) of AChE. Besides, this
compound also exhibited greater ability to inhibit advanced
glycation end products formation with additional radical
scavenging property. It (7m) also ameliorated scopolamine-
induced memory de cit in mice employing Morris water
maze test, at the dose of 2, 5 and 10 mg/kg. Thus, flavonoids
might be the promising lead compound as potential poly-
functional anti-Alzheimer’s agents.
e:
manjinder2007@gmail.comDesign, synthesis and biological evaluation of polyfunctional flavonoids: Anti-Alzheimer’s agents
Manjinder Singh
and
Om Silakari
Punjabi University, India