Chalcones (trans-1,3-diphenyl-2-propen-1-ones) form simple chemical structures that act as precursors for the biogenesis of flavonoids. These are distributed in plants and have two aromatic or heteroaromatic rings connected by a three-carbon α, β-unsaturated carbonyl group. Considering the importance of chalcones as monoamine oxidase and acetylcholinesterase inhibitors, the study was designed as a comprehensive and systematic analysis to evaluate the pharmacological activities leading to the formation of drug molecules against Alzheimer's disease (AD). Based on our previous research, 11 indolyl chalcones (IC1-IC11) were synthesised and investigated for MAO-B inhibitory activity. The inhibitory potential was evaluated based on binding and reversibility studies using purified enzymes. The active and most promising molecule, (2E)-3-(4-bromophenyl)-1-(1H-indol-3-yl) prop-2-en-1-one (IC9), also found predominant acetylcholinesterase inhibition and hence it was found dual acting in vitro. Based on this, the molecule IC9 was further subjected to cell line studies to further explore its role as a neuroprotective agent against neuronal degeneration, one of the main contributing parameters related to AD.
Keywords: Acetylcholinesterase; Alzheimer’s disease; Chalcones; Monoamine oxidase.
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