Inhibition of human plasma cholinesterase by malachite green and related triarylmethane dyes: Mechanistic implications

• Published in: Archives of biochemistry and biophysics 2005-08, Vol.440 (2), p.118-122
• Main Authors: Küçükkilinç, Tuba, Ozer, Inci
• Format: Article
• Language: English
• Subjects: Binding Sites; Butyrylthiocholine - chemistry; Butyrylthiocholine - metabolism; Choline - blood; Choline - metabolism; Cholinesterase Inhibitors - pharmacology; Cholinesterases - blood; Cholinesterases - drug effects; Cholinesterases - metabolism; Enzyme inhibition; Humans; Hydrogen-Ion Concentration; Indans - pharmacology; Kinetics; Ligands; Malachite green; Methyl green; Methyl Green - chemistry; Methyl Green - pharmacology; Pararosaniline; Peripheral Nerves - metabolism; Phenothiazines - pharmacology; Piperidines - pharmacology; Plasma cholinesterase; Propidium - pharmacology; Rosaniline Dyes - chemistry; Rosaniline Dyes - pharmacology; Temperature; Toluidines - chemistry; Toluidines - pharmacology; Triarylmethane dyes
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2005.06.003

The inhibitory effects of the cationic triarylmethane (TAM +) dyes, pararosaniline (PR +), malachite green (MG +), and methyl green (MeG +) on human plasma cholinesterase (BChE) were studied at 25 °C in 100 mM Mops, pH 8.0, with butyrylthiocholine as substrate. PR + and MG + caused linear mixed inhibition of enzyme activity. The respective inhibitory parameters were K i = 1.9 ± 0.23 μM, α = 13 ± 48, β = 0 and K i = 0.28 ± 0.037 μM, α = 23 ± 7.4, β = 0. MeG + acted as a competitive inhibitor with K i = 0.12 ± 0.017 μM ( α, ∞, β, not applicable). The K i values were within the same range reported for a number of ChE inhibitors including propidium ion, donepezil, and the phenothiazines, suggesting that TAM +s are active site ligands. On the other hand, the α values failed to correlate with values previously reported for a number of ChE inhibitors. It appears that mixed inhibition is the combined result of more than one type of binding and S–I interference. The impact of ligands at the choline-specific and peripheral anionic sites (or, possibly, accessory structural domains) on BChE activity needs to be studied in further detail.