Exploration of chromen-4-one based scaffold’s potential in Alzheimer’s disease: Design, Synthesis and Biological evaluations

Publication date: Available online 11 September 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Manjinder Singh, Maninder Kaur, Nirmal Singh, Om Silakari
A novel series of flavonoid based compounds were designed, synthesized and biologically evaluated for Acetylcholinesterase (AChE) inhibitory activity integrated with advanced glycation end products (AGEs) inhibitory and antioxidant ptential. Most of the derivatives inhibited AChE in nanomolar IC50 range along with good AGEs inhibitory and radical scavenging activity. Among them, 7m, strongly inhibited AChE (IC50=5.87 nM) and found to be potent as compared to the reference drug donepezil (IC50=12.7 nM). Its potent inhibitory activity has been justified by docking analysis that revealed its dual binding characteristic with both CAS (catalytic active site) and PAS (peripheral anionic site) of AChE, simultaneously. Additionally, this compound also displayed ability to prevent advanced glycation end products formation (IC50=23.0 µM) with additional radical scavenging property (IC50=37.12 nM). It (7m) also ameliorated scopolamine induced memory deficit in mice employing Morris water maze test. Thus, flavonoids might be the promising lead compounds as potential polyfunctional anti-Alzheimer's agents.

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