Design, synthesis and biological activity of 1H-indene-2-carboxamides as multi-targeted anti-Alzheimer agents. (2nd November 2016)

• Record Type: Journal Article
• Authors: Koca, Mehmet; Yerdelen, Kadir Ozden; Anil, Baris; Kasap, Zeynep; Sevindik, Handan; Ozyurek, Ibrahim; Gunesacar, Gulsen; Turkaydin, Kubra
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 31(2016:Apr.)Supplement 2
• Page Start: 13
• Page End: 23
• Publication Date: 2016-11-02
• Subjects: AChE -- Alzheimer -- Aβ1–42 -- BuChE -- molecular modeling; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2016.1186019
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: The aim of this study was to design new molecules and evaluate their anticholinesterase and amyloid beta (Aβ1–42 ) 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 Aβ1–42 aggregation. The results revealed that most compounds showed higher inhibitory activity against BuChE than AChE. Compounds20 and21 were found to be the most potent BuChE inhibitors with respective IC50 values of 1.08 and 1.09 μM. Compounds16, 20, 21 and22 exhibited remarkable inhibition of Aβ1–42 aggregation. Kinetic analysis showed that the most potent BuChE inhibitor (20 ) acted as a noncompetitive inhibitor. Docking studies suggested that inhibitor20 displayed many potential hydrogen-bondings with the PAS of BuChE. These results suggest that compound20 may be an especially promising multifunctional drug for the prevention and treatment of AD.