Inhibition of Acetylcholinesterase and Butyrylcholinesterase by a Plant Secondary Metabolite Boldine

. 2018 ; 2018 () : 9634349. [epub] 20180405

Jazyk angličtina Země Spojené státy americké Médium electronic-ecollection

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/pmid29850593

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are two enzymes sensitive to various chemical compounds having ability to bind to crucial parts of these enzymes. Boldine is a natural alkaloid and it was mentioned in some older works that it can inhibit some kinds of AChE. We reinvestigated this effect on AChE and also on BChE using acetyl (butyryl) thiocholine and Ellman's reagents as standard substances for spectrophotometric assay. We found out IC50 of AChE equal to 372 μmol/l and a similar level to BChE, 321 μmol/l. We conclude our experiment by a finding that boldine is cholinesterase inhibitor; however we report significantly weaker inhibition than that suggested in literature. Likewise, we tried to investigate the mechanism of inhibition and completed it with in silico study. Potential toxic effect on cholinesterases in real conditions is also discussed.

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Pohanka M. Cholinesterases, a target of pharmacology and toxicology. Biomedical Papers. 2011;155(3):219–230. doi: 10.5507/bp.2011.036. PubMed DOI

Pohanka M. Butyrylcholinesterase as a biochemical marker. Bratislava Medical Journal. 2013;114(12):726–734. doi: 10.4149/BLL_2013_153. PubMed DOI

Pohanka M. Acetylcholinesterase inhibitors: a patent review (2008 present) Expert Opinion on Therapeutic Patents. 2012;22(8):871–886. doi: 10.1517/13543776.2012.701620. PubMed DOI

Julian P. L., Pikl J. Studies in the indole series. III. On the synthesis of physostigmine. Journal of the American Chemical Society. 1935;57(3):539–544. doi: 10.1021/ja01306a046. DOI

Lilienfeld S. Galantamine—a novel cholinergic drug with a unique dual mode of action for the treatment of patients with Alzheimer's disease. CNS Drug Reviews. 2002;8(2):159–176. doi: 10.1111/j.1527-3458.2002.tb00221.x. PubMed DOI PMC

O'Brien P., Carrasco-Pozo C., Speisky H. Boldine and its antioxidant or health-promoting properties. Chemico-Biological Interactions. 2006;159(1):1–17. doi: 10.1016/j.cbi.2005.09.002. PubMed DOI

Speisky H., Cassels B. K. Boldo and boldine: an emerging case of natural drug development. Pharmacological Research. 1994;29(1):1–12. doi: 10.1016/1043-6618(94)80093-6. PubMed DOI

Mollataghi A., Coudiere E., Hadi A. H. A., et al. Anti-acetylcholinesterase, anti-α-glucosidase, anti-leishmanial and anti-fungal activities of chemical constituents of Beilschmiedia species. Fitoterapia. 2012;83(2):298–302. doi: 10.1016/j.fitote.2011.11.009. PubMed DOI

Eyer P., Worek F., Kiderlen D., et al. Molar absorption coefficients for the reduced ellman reagent: reassessment. Analytical Biochemistry. 2003;312(2):224–227. doi: 10.1016/S0003-2697(02)00506-7. PubMed DOI

Pettersen E. F., Goddard T. D., Huang C. C., et al. UCSF Chimera—a visualization system for exploratory research and analysis. Journal of Computational Chemistry. 2004;25(13):1605–1612. doi: 10.1002/jcc.20084. PubMed DOI

Dvir H., Silman I., Harel M., Rosenberry T. L., Sussman J. L. Acetylcholinesterase: from 3D structure to function. Chemico-Biological Interactions. 2010;187:10–22. PubMed PMC

Nicolet Y., Lockridge O., Masson P., Fontecilla-Camps J. C., Nachon F. Crystal structure of human butyrylcholinesterase and of its complexes with substrate and products. The Journal of Biological Chemistry. 2003;278(42):41141–41147. doi: 10.1074/jbc.M210241200. PubMed DOI

Pohanka M. Biosensors containing acetylcholinesterase and butyrylcholinesterase as recognition tools for detection of various compounds. Chemical Papers. 2015;69(1):4–16. doi: 10.2478/s11696-014-0542-x. DOI

Ellman G. L., Courtney K. D., Andres V., Jr., Featherstone R. M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical Pharmacology. 1961;7(2):88–95. doi: 10.1016/0006-2952(61)90145-9. PubMed DOI

Yang Z., Song Z., Xue W., et al. Synthesis and structure-Activity relationship of nuciferine derivatives as potential acetylcholinesterase inhibitors. Medicinal Chemistry Research. 2014;23(6):3178–3186. doi: 10.1007/s00044-013-0905-9. DOI

Marquis J. K. Pharmacological significance of acetylcholinesterase inhibition by tetrahydroaminoacridine. Biochemical Pharmacology. 1990;40(5):1071–1076. doi: 10.1016/0006-2952(90)90495-7. PubMed DOI

Wilkinson D. G. The pharmacology of donepezil: a new treatment for Alzheimer's disease. Expert Opinion on Pharmacotherapy. 1999;1(1):121–135. doi: 10.1517/14656566.1.1.121. PubMed DOI

Tang H., Wei Y.-B., Zhang C., et al. Synthesis, biological evaluation and molecular modeling of oxoisoaporphine and oxoaporphine derivatives as new dual inhibitors of acetylcholinesterase/butyrylcholinesterase. European Journal of Medicinal Chemistry. 2009;44(6):2523–2532. doi: 10.1016/j.ejmech.2009.01.021. PubMed DOI

Pecic S., McAnuff M. A., Harding W. W. Nantenine as an acetylcholinesterase inhibitor: SAR, enzyme kinetics and molecular modeling investigations. Journal of Enzyme Inhibition and Medicinal Chemistry. 2011;26(1):46–55. doi: 10.3109/14756361003671078. PubMed DOI PMC

Backhouse N., Delporte C., Givernau M., Cassels B. K., Valenzuela A., Speisky H. Anti-inflammatory and antipyretic effects of boldine. Agents and Actions Supplements. 1994;42(3-4):114–117. doi: 10.1007/BF01983475. PubMed DOI

Cermanova J., Prasnicka A., Dolezelova E., et al. Pharmacokinetics of boldine in control and mrp2-deficient rats. Physiological Research. 2016;65:S489–S497. PubMed

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