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

Abstract

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.

• Authors: Seda Onder, Kevser Biberoglu, Ozden Tacal
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 314 Pg. 108845 (Dec 01 2019) ISSN: 1872-7786 [Electronic] Ireland
• PMID: 31593690 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Cholinesterase Inhibitors
• Phenothiazines
• Acetylcholinesterase
• Butyrylcholinesterase
• methylene violet

Topics

• Acetylcholinesterase (chemistry, metabolism)
• Butyrylcholinesterase (chemistry, metabolism)
• Cholinesterase Inhibitors (chemistry, metabolism)
• Humans
• Kinetics
• Phenothiazines (chemistry, metabolism)