Toluidine blue O is a potent inhibitor of human cholinesterases

BİBEROĞLU K., TEK M. Y., GHASEMI S., TACAL Ö.

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, cilt.604, ss.57-62, 2016 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 604
  • Basım Tarihi: 2016
  • Doi Numarası: 10.1016/j.abb.2016.06.005
  • Dergi Adı: ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.57-62
  • Anahtar Kelimeler: Cholinesterases, Phenothiazines, Site-directed mutagenesis, Cholinesterase inhibition, Toluidine blue O, ALZHEIMERS-DISEASE, HUMAN BUTYRYLCHOLINESTERASE, METHYLENE-BLUE, AMYLOID-BETA, CATIONIC TRIARYLMETHANE, PHENOTHIAZINE DYES, DUAL INHIBITORS, ACETYLCHOLINESTERASE, DERIVATIVES, AGGREGATION
  • Hacettepe Üniversitesi Adresli: Evet

Özet

In this study, the inhibitory effects of three phenothiazines [toluidine blue O (TBO), thionine (TH) and methylene violet (MV)] were tested on human plasma butyrylcholinesterase (BChE) and their inhibitory mechanisms were studied in detail. MV acted as a linear mixed type inhibitor of human BChE with K-i = 0.66 +/- 0.06 mu M and alpha = 13.6 +/- 3.5. TBO and TH caused nonlinear inhibition of human BChE, compatible to double occupancy. K-i values estimated by nonlinear regression analysis for TBO and TH were 0.008 +/- 0.003 mu M and 2.1 +/- 0.42 mu M, respectively. The inhibitory potential of TBO was also tested on human erythrocyte AChE. TBO acted as a linear mixed type inhibitor of human AChE with K-i = 0.041 +/- 0.005 mu M and alpha = 1.6 +/- 0.007. Using four site-directed BChE mutants, the role of peripheral anionic site residues of human BChE was also investigated in the binding of TBO to BChE. The peripheral anionic site mutants of BChE caused 16-69-fold increase in K-i value of TBO, compared to recombinant wild-type, suggesting that peripheral anionic site residues are involved in the binding of TBO to human BChE. In conclusion, TBO which is a potent inhibitor of human cholinesterases, may be a potential drug candidate for the treatment of Alzheimer's disease. (C) 2016 Elsevier Inc. All rights reserved.