Title: Kinetics of human butyrylcholinesterase inhibition by 1,9-dimethyl-methylene blue Biberoglu K Ref: J Turkish chem soc sect chem, 8:435, 2021 : PubMed
Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disorder, characterized by beta-amyloid plaques, neurofibrillary tangles, and loss of cholinergic neurons. Butyrylcholinesterase (BChE) inhibition is a critical strategy for the treatment of AD since BChE causesinactivation of neurotransmitter acetylcholine and has positive effects on promoting the formation of beta-amyloidfibrils. Our previous studies showed that various phenothiazine-derived compounds such as thionineand toluidine blue O (TBO) cause a potent inhibition of human cholinesterases. TBO was also found to affect amyloid precursor protein processing in-vitro and in-vivo models of AD. In this study, it was aimed todetermine the inhibitory effect of 1,9-dimethyl-methylene blue (DMMB), a phenothiazine-derived compound,on human plasma BChE and explore its inhibitory mechanism. The inhibition of human BChE was assessedby the colorimetric method of Ellman using butyrylthiocholine as substrate and 0-0.375 microM of DMMB. Thekinetic findings showed that DMMB acts as a linear mixed-type inhibitor of human BChE with Ki value of 23 +/- 0.004 nM and alpha= 3.6 +/- 1.6. In conclusion, DMMB, which is a potent inhibitor effective at nM level, may behelpful in designing new cholinesterase inhibitors for the treatment of AD
