Inhibition of acetylcholinesterase and cholinesterase by ellipticine derivatives

Ellipticine and its derivatives are indole alkaloids with antitumoral properties. The cytotoxicity of ellipticines may be related to their affinity for deoxyribonucleic acid to which they combined by intercalation. Elliptinium acetate, a quaternary ammonium derivative, has induced remissions in patients with breast cancer and other malignancies. Some of the side effects observed, such as dyspnea and muscle cramps, suggested an interaction between elliptinium and the cholinergic system. Previous studies on the structure-activity relationship have shown that many reversible inhibitors of acetylcholinesterase (EC 3.1.1.7, AcChE) and butyryl cholinesterase (EC 3.1.1.8, BuChE) contain one or two quaternary ammonium groups, or eventually a protonate tertiary amine. The present study reports the interaction of ellipticine derivatives with the catalytic activity of acetylcholinesterase from rat brain and of human sera pseudocholinesterase.