Synthesis and characterization of new chalcone derivatives as acetylcholinesterase inhibitor

Abstract

Chalcones are open-chain flavonoids and considered to be precursors of isoflavonoids and flavonoids which consist of two aromatic rings that linked by a three carbon consist of a, ß-unsaturated carbonyl system. Besides, chalcones display a wide range of biological activities such as antibacterial, anticancer, antioxidant including AChE inhibition activities. Super-activation of cholinesterase (acetylcholinesterase) is linked to various neurological problems most precisely Alzheimer’s disease (AD), which leads to senile dementia. Therefore, cholinesterase (AChE) inhibition is considered as a promising strategy for the treatment of Alzheimer’s disease. For this purpose, this study focused on the synthesis of a series of new chalcone derivatives with anti-cholinesterase potential. In the first step of this study 1-(4-(benzyloxy)phenyl)ethan-1-one (51) was successfully synthesized by benzylation of 4-hydroxy acetophenone with a yield of 88.49% as a precursor to synthesize a series of chalcone derivatives. Then, the precursor was reacted with benzaldehyde derivatives (52a-f) with different substituent groups on its para position (4-H, 4-Br, 4-NO2, 4-isopropyl, 4-OCH3, and 4-Cl), respectively, by base-catalyzed Claisen-Schmidt condensation reaction to produce a series of new chalcone derivatives (53a-f). The yield of synthesized compounds were (50-58%), and their molecular structures were confirmed using IR, 1H NMR and 13C NMR analysis. The synthesized chalcone derivatives (53a-f) were tested against AChE. All compounds showed good activity in AChE inhibition. Moreover, compounds with the presence of electron-withdrawing groups (53b, 53c and 53f) showed excellent activity in AChE inhibition, Among them, compound (53c) showed the most potent activity (89.44%) in acetylcholinesterase inhibition which quite near from the result of the standard Galantamine (94.11%).Chalcones are open-chain flavonoids and considered to be precursors of isoflavonoids and flavonoids which consist of two aromatic rings that linked by a three carbon consist of a, ß-unsaturated carbonyl system. Besides, chalcones display a wide range of biological activities such as antibacterial, anticancer, antioxidant including AChE inhibition activities. Super-activation of cholinesterase (acetylcholinesterase) is linked to various neurological problems most precisely Alzheimer’s disease (AD), which leads to senile dementia. Therefore, cholinesterase (AChE) inhibition is considered as a promising strategy for the treatment of Alzheimer’s disease. For this purpose, this study focused on the synthesis of a series of new chalcone derivatives with anti-cholinesterase potential. In the first step of this study 1-(4-(benzyloxy)phenyl)ethan-1-one (51) was successfully synthesized by benzylation of 4-hydroxy acetophenone with a yield of 88.49% as a precursor to synthesize a series of chalcone derivatives. Then, the precursor was reacted with benzaldehyde derivatives (52a-f) with different substituent groups on its para position (4-H, 4-Br, 4-NO2, 4-isopropyl, 4-OCH3, and 4-Cl), respectively, by base-catalyzed Claisen-Schmidt condensation reaction to produce a series of new chalcone derivatives (53a-f). The yield of synthesized compounds were (50-58%), and their molecular structures were confirmed using IR, 1H NMR and 13C NMR analysis. The synthesized chalcone derivatives (53a-f) were tested against AChE. All compounds showed good activity in AChE inhibition. Moreover, compounds with the presence of electron-withdrawing groups (53b, 53c and 53f) showed excellent activity in AChE inhibition, Among them, compound (53c) showed the most potent activity (89.44%) in acetylcholinesterase inhibition which quite near from the result of the standard Galantamine (94.11%).