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

Year 2021, , 435 - 442, 31.05.2021

Kevser Bıberoglu

https://doi.org/10.18596/jotcsa.853598

Abstract

Alzheimer’s disease (AD) is an irreversible and progressive neurodegenerative disorder, characterized by β-amyloid plaques, neurofibrillary tangles and loss of cholinergic neurons. Butyrylcholinesterase (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 (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 (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

Alzheimer’s disease, butyrylcholinesterase, 1,9-dimethyl-methylene blue, cholinesterase inhibition, phenothiazine

References

• 1. Taylor P, Radić Z. The cholinesterases: from genes to proteins. Annu Rev Pharmacol Toxicol. 1994;34:281-320.
• 2. Masson P, Rochu D. Catalytic bioscavengers against toxic esters, an alternative approach for prophylaxis and treatments of poisonings. Acta Naturae. 2009;1(1):68-79.
• 3. Nicolet Y, Lockridge O, Masson P, Fontecilla-Camps JC, Nachon F. Crystal structure of human butyrylcholinesterase and of its complexes with substrate and products. J Biol Chem. 2003;278(42):41141-7.
• 4. Darvesh S, Hopkins DA, Geula C. Neurobiology of butyrylcholinesterase. Nat Rev Neurosci. 2003;4(2):131-8.
• 5. Zvěřová M. Clinical aspects of Alzheimer's disease. Clin Biochem. 2019;72:3-6.
• 6. LaFerla FM, Oddo S. Alzheimer's disease: Abeta, tau and synaptic dysfunction. Trends Mol Med. 2005;11(4):170-6.
• 7. Perry EK, Perry RH, Blessed G, Tomlinson BE. Changes in brain cholinesterases in senile dementia of Alzheimer type. Neuropathol Appl Neurobiol. 1978;4(4):273-7.
• 8. Ferreira-Vieira TH, Guimaraes IM, Silva FR, Ribeiro FM. Alzheimer's disease: Targeting the Cholinergic System. Curr Neuropharmacol. 2016;14(1):101-15.
• 9. Mesulam MM. Cholinergic circuitry of the human nucleus basalis and its fate in Alzheimer's disease. J Comp Neurol. 2013;521(18):4124-44.
• 10. Yiannopoulou KG, Papageorgiou SG. Current and future treatments for Alzheimer's disease. Ther Adv Neurol Disord. 2013;6(1):19-33.
• 11. Geula C, Mesulam MM. Cholinesterases and the pathology of Alzheimer disease. Alzheimer disease and associated disorders. 1995;9 Suppl 2:23-8.
• 12. Nordberg A. Mechanisms behind the neuroprotective actions of cholinesterase inhibitors in Alzheimer disease. Alzheimer Dis Assoc Disord. 2006;20(2 Suppl 1):S12-8.
• 13. Longo FM, Massa SM. Neuroprotective strategies in Alzheimer's disease. NeuroRx. 2004;1(1):117-27.
• 14. Sezgin Z, Biberoglu K, Chupakhin V, Makhaeva GF, Tacal O. Determination of binding points of methylene blue and cationic phenoxazine dyes on human butyrylcholinesterase. Arch Biochem Biophys. 2013;532(1):32-8.
• 15. Biberoglu K, Tek MY, Ghasemi ST, Tacal O. Toluidine blue O is a potent inhibitor of human cholinesterases. Arch Biochem Biophys. 2016;604:57-62.
• 16. Yuksel M, Biberoglu K, Onder S, Akbulut KG, Tacal O. Effects of phenothiazine-structured compounds on APP processing in Alzheimer's disease cellular model. Biochimie. 2017;138:82-9.
• 17. Yuksel M, Biberoglu K, Onder S, Akbulut KG, Tacal O. Toluidine blue O modifies hippocampal amyloid pathology in a transgenic mouse model of Alzheimer's disease. Biochimie. 2018;146:105-12.
• 18. Taniguchi S, Suzuki N, Masuda M, Hisanaga S, Iwatsubo T, Goedert M, et al. Inhibition of heparin-induced tau filament formation by phenothiazines, polyphenols, and porphyrins. J Biol Chem. 2005;280(9):7614-23.
• 19. Varga B, Csonka Á, Csonka A, Molnár J, Amaral L, Spengler G. Possible Biological and Clinical Applications of Phenothiazines. Anticancer Res. 2017;37(11):5983-93.
• 20. Ford JM, Prozialeck WC, Hait WN. Structural features determining activity of phenothiazines and related drugs for inhibition of cell growth and reversal of multidrug resistance. Mol Pharmacol. 1989;35(1):105-15.
• 21. Jaszczyszyn A, Gąsiorowski K, Świątek P, Malinka W, Cieślik-Boczula K, Petrus J, et al. Chemical structure of phenothiazines and their biological activity. Pharmacol Rep. 2012;64(1):16-23.
• 22. Weiss B, Prozialeck WC, Wallace TL. Interaction of drugs with calmodulin. Biochemical, pharmacological and clinical implications. Biochem Pharmacol. 1982;31(13):2217-26.
• 23. Fourrier A, Gasquet I, Allicar MP, Bouhassira M, Lépine JP, Bégaud B. Patterns of neuroleptic drug prescription: a national cross-sectional survey of a random sample of French psychiatrists. Br J Clin Pharmacol. 2000;49(1):80-6.
• 24. Choi JH, Yang YR, Lee SK, Kim SH, Kim YH, Cha JY, et al. Potential inhibition of PDK1/Akt signaling by phenothiazines suppresses cancer cell proliferation and survival. Ann N Y Acad Sci. 2008;1138:393-403.
• 25. Augustinsson K-B. Methylene blue as an inhibitor of acetylcholine-esterase. Acta Chem Scand. 1950;4:536-42.
• 26. Wischik C, Staff R. Challenges in the conduct of disease-modifying trials in AD: practical experience from a phase 2 trial of Tau-aggregation inhibitor therapy. J Nutr Health Aging. 2009;13(4):367-9.
• 27. Biberoglu K, Tacal Ö, Akbulut H. The role of Phe329 in binding of cationic triarylmethane dyes to human butyrylcholinesterase. Arch Biochem Biophys. 2011;511(1-2):64-8.
• 28. Ellman GL, Courtney KD, Andres V, Jr., Feather-Stone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961;7:88-95.
• 29. Segel IH. Enzyme kinetics: behavior and analysis of rapid equilibrium and steady state enzyme systems: Wiley New York:; 1975.
• 30. Lane RM, Potkin SG, Enz A. Targeting acetylcholinesterase and butyrylcholinesterase in dementia. Int J Neuropsychopharmacol. 2006;9(1):101-24.
• 31. Greig NH, Utsuki T, Ingram DK, Wang Y, Pepeu G, Scali C, et al. Selective butyrylcholinesterase inhibition elevates brain acetylcholine, augments learning and lowers Alzheimer beta-amyloid peptide in rodent. Proc Natl Acad Sci U S A. 2005;102(47):17213-8.
• 32. Guillozet AL, Smiley JF, Mash DC, Mesulam MM. Butyrylcholinesterase in the life cycle of amyloid plaques. Ann Neurol. 1997;42(6):909-18.
• 33. Reid GA, Darvesh S. Butyrylcholinesterase-knockout reduces brain deposition of fibrillar β-amyloid in an Alzheimer mouse model. Neuroscience. 2015;298:424-35.
• 34. Li B, Stribley JA, Ticu A, Xie W, Schopfer LM, Hammond P, et al. Abundant tissue butyrylcholinesterase and its possible function in the acetylcholinesterase knockout mouse. J Neurochem. 2000;75(3):1320-31.
• 35. Perry EK, Tomlinson BE, Blessed G, Bergmann K, Gibson PH, Perry RH. Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J. 1978;2(6150):1457-9.
• 36. Arendt T, Brückner MK, Lange M, Bigl V. Changes in acetylcholinesterase and butyrylcholinesterase in Alzheimer's disease resemble embryonic development--a study of molecular forms. Neurochem Int. 1992;21(3):381-96.
• 37. Gupta RK, editor Phenothiazines and 1,4-benzothiazines : chemical and biomedical aspects1988.
• 38. Keyzer H. Thiazines and structurally related compounds. 1992.
• 39. Pfaffendorf M, Bruning TA, Batnik HD, van Zwieten PA. The interaction between methylene blue and the cholinergic system. Br J Pharmacol. 1997;122(1):95-8.
• 40. Oz M, Lorke DE, Hasan M, Petroianu GA. Cellular and molecular actions of Methylene Blue in the nervous system. Med Res Rev. 2011;31(1):93-117.
• 41. Ehrlich P. Ueber die Methylenblaureaction der lebenden Nervensubstanz. DMW-Deutsche Medizinische Wochenschrift. 1886;12(04):49-52.
• 42. Taylor KB, Jeffree GM. A new basic metachromatic dye, 1∶9-Dimethyl Methylene Blue. The Histochemical Journal. 1969;1(3):199-204.
• 43. Mohammad T, Morrison H. Photonuclease activity of Taylor's blue. Bioorg Med Chem Lett. 1999;9(15):2249-54.
• 44. Pereira LM, Mota CM, Baroni L, Bronzon da Costa CM, Brochi JCV, Wainwright M, et al. Inhibitory action of phenothiazinium dyes against Neospora caninum. Scientific Reports. 2020;10(1):7483.
• 45. Delport A, Harvey BH, Petzer A, Petzer JP. The monoamine oxidase inhibition properties of selected structural analogues of methylene blue. Toxicol Appl Pharmacol. 2017;325:1-8.
• 46. Santos DA, Crugeira PJL, Nunes IPF, de Almeida PF, Pinheiro ALB. A novel technique of antimicrobial photodynamic therapy - aPDT using 1,9-dimethyl-methylene blue zinc chloride double salt-DMMB and polarized light on Staphylococcus aureus. J Photochem Photobiol B. 2019;200:111646.
• 47. Küçükkilinç T, Ozer I. Multi-site inhibition of human plasma cholinesterase by cationic phenoxazine and phenothiazine dyes. Archives of biochemistry and biophysics. 2007;461(2):294-8.
• 48. Harrington CR, Storey JM, Clunas S, Harrington KA, Horsley D, Ishaq A, et al. Cellular Models of Aggregation-dependent Template-directed Proteolysis to Characterize Tau Aggregation Inhibitors for Treatment of Alzheimer Disease. J Biol Chem. 2015;290(17):10862-75.
• 49. Biberoglu K, Yuksel M, Tacal O. Azure B affects amyloid precursor protein metabolism in PS70 cells. Chem Biol Interact. 2019;299:88-93.