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

Onder S., Biberoglu K., Tacal Ö.

CHEMICO-BIOLOGICAL INTERACTIONS, cilt.314, 2019 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 314
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1016/j.cbi.2019.108845
  • Dergi Adı: CHEMICO-BIOLOGICAL INTERACTIONS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Anahtar Kelimeler: Acetylcholinesterase, Butyrylcholinesterase, Methylene violet 3RAX, Cholinesterase inhibition, TOLUIDINE BLUE O, ALZHEIMERS-DISEASE, CHOLINESTERASE-INHIBITORS, CATIONIC TRIARYLMETHANE, CHOLINERGIC SYSTEM, MOUSE MODEL, DERIVATIVES, BINDING, SITE, DYES
  • Hacettepe Üniversitesi Adresli: Evet

Özet

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 K-i value of 1.58 +/- 0.36 mu M; alpha = 1; beta = 0.12 +/- 0.0003. On the other hand, it caused linear competitive inhibition of BChE with K-i value of 0.51 +/- 0.006 mu M; alpha = infinity. In conclusion, methylene violet 3RAX which is a highly effective inhibitor of both human AChE and human BChE with K-i values in low micromolar range may be a promising candidate for the treatment of Alzheimer's disease.