Preparation, anticholinesterase activity, and docking study of new 2-butenediamide and oxalamide derivatives. (August 2015)

• Record Type: Journal Article
• Authors: Yerdelen, Kadir Ozden; Koca, Mehmet; Kasap, Zeynep; Anil, Baris
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 30:Number 4(2015:Aug.)
• Page Start: 671
• Page End: 678
• Publication Date: 2015-08
• Subjects: Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.3109/14756366.2014.959947
• Languages: English
• ISSNs: 1475-6366

Abstract

<abstract> <title>Abstract</title> <p>Several new oxalamide and 2-butenediamide derivatives have been designed, synthesized and evaluated as the acetyl- and butyryl-cholinesterase inhibitors for Alzheimer's disease. The enzyme inhibitory activity of the synthesized compounds was measured using Ellman's colorimetric method. It was revealed that compound <bold>1a</bold> (<italic>N, N′-bis-(4-chloro-benzyl)-N, N′-diphenyl-oxalamide</italic>) showed maximum activity against BuChE with a half maximal inhibitory concentration (IC₅₀) = 1.86 µM and compound <bold>2a</bold> (<italic>but-2-enedioic acid bis-[(4-chloro-benzyl)-phenyl-amide]</italic>) exhibited optimum AChE (IC₅₀ = 1.51 µM) inhibition with a high-selectivity index. To better understand the enzyme–inhibitor interaction of the most active compounds towards cholinesterase, molecular modelling studies were carried out. Docking simulations revealed that inhibitors <bold>1a</bold> and <bold>2a</bold> targeted both the catalytic active site and the peripheral anionic site of 1ACJ and 1P0I.</p> </abstract>