Akademik Veri Yönetim Sistemi
LATIN AMERICAN JOURNAL OF PHARMACY, cilt.34, sa.5, ss.924-933, 2015 (SCI-Expanded)
A series of new oxalamide (1-15) derivatives were synthesized and evaluated as dual cholinesterase inhibitors for Alzheimer's disease. The anticholinesterase activity of oxalamide derivatives was determined against Electric Eel acetylcholinesterase (EeAChE) and horse serum butyrylcholinesterase (hBuChE) and some of the compounds appeared as moderately potent inhibitors of EeAChE and hBuChE. The compound 13 (N, N'-dibenzyl- N, N'-bis-(4-chloro-phenyl)-oxalamide) showed maximum activity against hBuChE with an half maximal inhibitory concentration (IC50) = 1.19 mu M whereas the compound 12 (N, N'-dibenzyl-N, N'-bis-(4-fluorophenyl)-oxalamide) exhibited optimum dual ChE (AChE IC50= 8.31 mu M, BuChE IC50= 1.34 mu M) inhibition. To better understand the enzyme-inhibitor interaction of the most active compounds towards cholinesterases, molecular modeling studies were carried out on high-resolution crystallographic structures. The docking simulation showed that the compounds 11 and 13 created many hydrogen bond and p-p stacking interactions with the catalytic and the peripheral anionic site gorges of 1ACJ and 1P0I, confirming its high inhibitor potency and supporting the mixed-type inhibition.