Table of Contents
ISRN Pharmacology
Volume 2012, Article ID 707932, 11 pages
http://dx.doi.org/10.5402/2012/707932
Research Article

Pharmacological Evaluation and Docking Studies of 3-Thiadiazolyl- and Thioxo-1,2,4-triazolylcoumarin Derivatives as Cholinesterase Inhibitors

1Department of Pharmaceutical Sciences, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan
2Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan
3Zhang Initiative Research Unit, Advanced Science Institute, RIKEN, 2-1 Hirosawa, Saitama, Wako 351-0198, Japan

Received 6 April 2012; Accepted 17 May 2012

Academic Editors: R. J. Beninger, M. C. Olianas, M. Tohda, and R. Trullas

Copyright © 2012 Ahsan Raza et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is considered a promising strategy for the treatment of Alzheimer’s disease (AD). This research project aims to provide a comprehensive knowledge of newly synthesized coumarin analogues with anti-AD potential. In the present work a series of 3-thiadiazolyl- and thioxo-1,2,4-triazolylcoumarins derivatives were designed, synthesized, and tested as potent inhibitors of cholinesterases. These compounds were assayed against AChE from electrophorus electricus and rabbit; and BChE from horse serum and rabbit by Ellman’s method using neostigmine methylsulphate and donepezil as reference drugs. Some of the assayed compounds proved to be potent inhibitors of AChE and BChE with 𝐾 𝑖 values in the micromolar range. 4b was found to be the most active compound with 𝐾 𝑖 value 0 . 0 2 8 Β± 0 . 0 0 2 μM and higher selectivity for AChE/BChE. The ability of 4b to interact with AChE was further confirmed through computational studies, in which a primary binding was proved to occur at the active gorge site, and a secondary binding was revealed at the peripheral anionic site. Structure activity relationships of prepared compounds were also discussed.