+441518081136Design, synthesis and biological evaluation of polyfunctional flavonoids: Anti-Alzheimer′s agents
4th International Congress on Drug Discovery, Designing and Development & International Conference and Exhibition on Biochemistry, Molecular Biology: R&D
November 02-03, 2017 Chicago, USA
Manjinder Singh and Om Silakari
Punjabi University, India
Posters & Accepted Abstracts : J Pharmacol Ther Res
Abstract:
Alzheimer’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 IC50 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 scopolamineinduced memory deficit 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 polyfunctional anti-Alzheimer’s agents.
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