Design, synthesis and biological activity of 1H-indene-2-carboxamides as multi-targeted anti-Alzheimer agents

作者：Koca Mehmet; Yerdelen Kadir Ozden; Anil Baris; Kasap Zeynep; Sevindik Handan; Ozyurek Ibrahim; Gunesacar Gulsen; Turkaydin Kubra

来源：Journal of Enzyme Inhibition and Medicinal Chemistry, 2016, 31(sup2): 13-23.

DOI：10.1080/14756366.2016.1186019

• AChE
• Alzheimer
• A1-42
• BuChE
• molecular modeling

The aim of this study was to design new molecules and evaluate their anticholinesterase and amyloid beta (A(1-42)) inhibition activities as multifunctional drug candidates for the treatment of Alzheimer's disease (AD). A series of 5,6-dimethoxy-1H-indene-2-carboxamides (1-22) was synthesized; cholinesterase inhibitory activities of the compounds were measured according to Ellman's colorimetric assay, while the thioflavin T assay was used for measuring the inhibition of A(1-42) aggregation. The results revealed that most compounds showed higher inhibitory activity against BuChE than AChE. Compounds 20 and 21 were found to be the most potent BuChE inhibitors with respective IC50 values of 1.08 and 1.09M. Compounds 16, 20, 21 and 22 exhibited remarkable inhibition of A(1-42) aggregation. Kinetic analysis showed that the most potent BuChE inhibitor (20) acted as a noncompetitive inhibitor. Docking studies suggested that inhibitor 20 displayed many potential hydrogen-bondings with the PAS of BuChE. These results suggest that compound 20 may be an especially promising multifunctional drug for the prevention and treatment of AD.

• 出版日期2016-12