Synthesis and biological evaluation of 3-triazolyl-coumarin derivatives as acetylcholinesterase and β-Amyloid aggregation inhibitors

Abstract

Five new 3-triazolyl-coumarin derivatives (C1-C5) were designed and synthesized as duo-actions, acetylcholinesterase and β-amyloid aggregation inhibitors, for the effective treatment of Alzheimer's disease. All compounds were synthesized using click reaction and obtained in moderate to high yield (ranging from 44 to 80%). The modified Ellman and Thioflavin T fluorescence methods were used for screening acetylcholinesterase and β-amyloid aggregation inhibitors activities, respectively. Among the test compounds, only C3 displayed high potency against Aβ1-42 aggregation with inhibition value of 79%. They interference of Aβ aggregation process of the best inhibitor, C3, was described by a molecular docking study using Discovery Studio ® program. It was observed that coumarin ring of C3 formed ㅠ-ㅠ interaction with Phe19 which involved intramolecular Aβ fibril formation. Unfortunately, the anti-AChE of C3 was not attractive since the inhibition value of 16% was observed. Last but not least, this study demonstrates the potent Aβ aggregation inhibitors, the newly synthesized C3, could be a promising candidate for the development of lead molecule against Alzheimer's disease.