Structural basis of acetylcholinesterase inhibition by triterpenoidal alkaloids

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• 作者：Khalid ; Asaad ; Azim ; M. Kamran ; Parveen ; Shehnaz ; Atta-ur-Rahman ; Choudhary ; M. Iqbal
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2005
• 出版时间：June 17, 2005
• 年：2005
• 卷：331
• 期：4
• 页码：1528-1532
• 全文大小：408 K

文摘

Acetylcholinesterase plays a crucial role in the metabolism of neurotransmitter, acetylcholine. Inhibition of Torpedo californica acetylcholinesterase by triterpenoidal alkaloids buxamine-B (1) and buxamine-C (2) has been studied by enzyme kinetics and molecular docking experiments. Buxamine-C (2) has been found to be 20-fold potent than buxamine-B (1) (K_i = 5.5 and 110 μM, respectively). The ligand docking experiments predicted that the cyclopentanophenanthrene skeleton of both inhibitors properly fits into the aromatic gorge of the enzyme. The C-3 and C-20 amino groups of both alkaloids mimic the well-known bis-quaternary ammonium inhibitors such as decamethonium and interact with Trp84 and Trp279 residues of the enzyme, respectively. The C-3 amino group in buxamine-C (2) appears to be better positioned at the bottom of the aromatic gorge and thus seems to be crucial for the inhibitory activity of such inhibitors.