The kinetics of inhibition of human acetylcholinesterase and butyrylcholinesterase by methylene violet 3RAX

• Published in: Chemico-biological interactions 2019-12, Vol.314, p.108845-108845, Article 108845
• Main Authors: Onder, Seda, Biberoglu, Kevser, Tacal, Ozden
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase; Butyrylcholinesterase; Cholinesterase inhibition; Methylene violet 3RAX
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2019.108845

Phenazines, naturally produced by bacteria and archaeal Methanosarcina species are nitrogen-containing tricyclic molecules with antibiotic, antitumoral, and antiparasitic activities. Phenazines are used as electron acceptors-donors in wide range of fields including environmental biosensors. In this study, the inhibitory effects of a synthetic phenazine dye, methylene violet 3RAX (also known as diethyl safranine) on human erythrocyte AChE and human plasma BChE were tested and also its inhibitory mechanisms for both enzymes were studied in detail. Kinetic analyses showed that methylene violet 3RAX acts as a hyperbolic noncompetitive inhibitor of AChE with Ki value of 1.58 ± 0.36 μM; α = 1; β = 0.12 ± 0.0003. On the other hand, it caused linear competitive inhibition of BChE with Ki value of 0.51 ± 0.006 μM; α = ∞. In conclusion, methylene violet 3RAX which is a highly effective inhibitor of both human AChE and human BChE with Ki values in low micromolar range may be a promising candidate for the treatment of Alzheimer's disease. •Methylene violet 3RAX is a cationic phenazine-structured dye.•Methylene violet 3RAX acts as a linear competitive inhibitor of human BChE.•Methylene violet 3RAX acts as a hyperbolic noncompetitive inhibitor of human AChE.•Methylene violet 3RAX may be a promising candidate for symptomatic AD treatment.