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

Authors :
Koca, Mehmet
Yerdelen, Kadir Ozden
Anil, Baris
Kasap, Zeynep
Sevindik, Handan
Ozyurek, Ibrahim
Gunesacar, Gulsen
Turkaydin, Kubra
Source :
Journal of Enzyme Inhibition & Medicinal Chemistry; 2016 Supplement, Vol. 31, p13-23, 11p
Publication Year :
2016

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 Aβ1–42aggregation. The results revealed that most compounds showed higher inhibitory activity against BuChE than AChE. Compounds20and21were found to be the most potent BuChE inhibitors with respective IC50values of 1.08 and 1.09 μM. Compounds16,20,21and22exhibited remarkable inhibition of Aβ1–42aggregation. Kinetic analysis showed that the most potent BuChE inhibitor (20) acted as a noncompetitive inhibitor. Docking studies suggested that inhibitor20displayed many potential hydrogen-bondings with the PAS of BuChE. These results suggest that compound20may be an especially promising multifunctional drug for the prevention and treatment of AD. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
14756366
Volume :
31
Database :
Complementary Index
Journal :
Journal of Enzyme Inhibition & Medicinal Chemistry
Publication Type :
Academic Journal
Accession number :
119997281
Full Text :
https://doi.org/10.1080/14756366.2016.1186019