Synthesis and inhibitory potential towards acetylcholinesterase, butyrylcholinesterase and lipoxygenase of some variably substituted chalcones

Abstract

A series of variably substituted chalcones were synthesized by condensation of substituted acetophenones with mono-, di- or trisubstituded benzaldehydes. It was observed that some of these compounds have the potential to inhibit acetylcholinesterase, whereas others show activity against butyrylcholinesterase, depending on the substitution pattern at the two aromatic rings of these chalcones. Similarly, lipoxygenase was inhibited by two of these compounds. It has been observed that inhibition of the three enzymes was concentration dependent with the IC50 values ranging from 28.2-134.5 microM against acetylcholinesterase, 16.0-23.1 microM against butyrylcholinesterase and 57.6-71.7 microM against lipoxygenase, respectively.

Design, synthesis and biological activity of multifunctional α,β-unsaturated carbonyl scaffolds for Alzheimer’s disease

“…Chalcone 22 and coumarin 23 derivatives have been described as AChE and BuChE inhibitors. While coumarins have also been applied as Aβ aggregation inhibitors, 24 chalcones are more commonly used as Aβ imaging agents.…”

“…22-26 In an attempt to combine these activities in a single chemical structure and develop multifunctional anti-AD compounds we synthesized 22 compounds with chalcone and coumarin head and varied tail groups. The aim was to build compounds of sufficient length to span the active center of the cholinesterases and at the same time interfere with Aβ self-assembly.…”

Simple chalcones and bis-chalcones ethers as possible pleiotropic agents

“…Due to the enone system, such molecules present relatively low redox potentials and have a greater probability of undergoing electron transfer reactions. They possess an extended number of biological activities: regulate cholesterol levels, reduce blood pressure, regulate blood sugar, improve vision and memory, inhibit acetylcholinesterase, inhibit enzymes implicated in inflammation, reduce joint and muscular pains, enhance liver and kidney functions, aid sleep, prevent cancer, strengthen the immune system and beautify the skin and hair 1,2 . Hydroxyl chalcones embrace hydroxyl substitution, a key group to greatly enhance the antioxidant activity of chalcones, due to their conversion to phenoxy radicals through the hydrogen atom transfer mechanism 3 .…”

Comparison of the inhibitory potential towards carbonic anhydrase, acetylcholinesterase and butyrylcholinesterase of chalcone and chalcone epoxide

“…These activities have been related to their flexible structure, which probably allows effective binding to enzymes and receptors. However, few investigations have been reported on their inhibiting potential towards AChE and BuChE . The epoxidation of chalcones, which furnishes useful building blocks in organic and pharmaceutical chemistry, has also not been extensively investigated for its biological activities.…”