Kinetics of human butyrylcholinesterase inhibition by 1,9-dimethyl-methylene blue

Authors : Kevser BIBEROGLU

Pages : 435-442

Doi:10.18596/jotcsa.853598

View : 12 | Download : 6

Publication Date : 2021-05-31

Article Type : Research Paper

Abstract :Alzheimer’s disease insert ignore into journalissuearticles values(AD); is an irreversible and progressive neurodegenerative disorder, characterized by β-amyloid plaques, neurofibrillary tangles and loss of cholinergic neurons. Butyrylcholinesterase insert ignore into journalissuearticles values(BChE); inhibition is one of the most critical strategy for the treatment of AD since BChE causes inactivation of neurotransmitter acetylcholine and has positive effects on promoting the formation of β-amyloid fibrils. Our previous studies showed that various phenothiazine-derived compounds such as thionine and toluidine blue O insert ignore into journalissuearticles values(TBO); cause a potent inhibition of human cholinesterases. TBO was also found to reduce amyloid precursor protein processing in-vitro and in-vivo models of AD. In this study, it was aimed to determine the inhibitory effect of 1,9-dimethyl-methylene blue insert ignore into journalissuearticles values(DMMB);, a phenothiazine-derived compound, on human plasma BChE and explore its inhibitory mechanism. The inhibition of human BChE was assessed by the colorimetric method of Ellman using butyrylthiocholine as substrate and 0-0.375 μM of DMMB. The kinetic findings showed that DMMB acts as a linear mixed-type inhibitor of human BChE with Ki value of 23 ± 0.004 nM and α= 3.6 ± 1.6. It was concluded that DMMB, which is a potent inhibitor effective at nM level may be helpful in designing new cholinesterase inhibitors for the treatment of AD.
Keywords : Alzheimers disease, butyrylcholinesterase, 1, 9 dimethyl methylene blue, cholinesterase inhibition, phenothiazine