The catechol-O-methyltransferase inhibitory potential of Z-vallesiachotamine by in silico and in vitro approaches

Abstract

Z-Vallesiachotamine is a monoterpene indole alkaloid that has a β-N-acrylate group in its structure. This class of compounds has already been described in different Psychotria species. Our research group observed that E/Z-vallesiachotamine exhibits a multifunctional feature, being able to inhibit targets related to neurodegeneration, such as monoamine oxidase A, sirtuins 1 and 2, and butyrylcholinesterase enzymes. Aiming at better characterizing the multifunctional profile of this compound, its effect on cathecol-O-methyltransferase activity was investigated. The cathecol-O-methyltransferase activity was evaluated in vitro by a fluorescence-based method, using S-(5′-adenosyl)-l-methionine as methyl donor and aesculetin as substrate. The assay optimization was performed varying the concentrations of methyl donor (S-(5′-adenosyl)-l-methionine) and enzyme. It was observed that the highest concentrations of both factors (2.25 U of the enzyme and 100 ′M of S-(5′-adenosyl)-l-methionine) afforded the more reproducible results. The in vitro assay demonstrated that Z-vallesiachotamine was able to inhibit the cathecol-O-methyltransferase activity with an IC50 close to 200 ′M. Molecular docking studies indicated that Z-vallesiachotamine can bind the catechol pocket of catechol-O-methyltransferase enzyme. The present work demonstrated for the first time the inhibitory properties of Z-vallesiachotamine on cathecol-O-methyltransferase enzyme, affording additional evidence regarding its multifunctional effects in targets related to neurodegenerative diseases.

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Acknowledgements

This work was supported by CNPq (grant #478496/2011-7) and by FAPERGS (grant #2281-2551/14-2SIAFEM). LCKJ and ATH thank CNPq for the fellowships. JMMA thanks to CAPES for the PhD scholarship.

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CSP (Postdoctoral Researcher) performed the in silico experiments and part of the in vitro method optimization. LCKJ (PhD Student) performed the in vitro experiments and wrote the paper. JMMA (PhD Student) performed part of the in vitro experiments. Both CSP and JMMA contributed to write the manuscript. CM and ATH supervised the experimental work and contributed to the manuscript. All the authors have read the final manuscript and approved the submission.

Corresponding author

Correspondence to Amélia Teresinha Henriques.

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dos Santos Passos, C., Klein-Júnior, L.C., de Mello Andrade, J.M. et al. The catechol-O-methyltransferase inhibitory potential of Z-vallesiachotamine by in silico and in vitro approaches. Rev. Bras. Farmacogn. 25, 382–386 (2015). https://doi.org/10.1016/j.bjp.2015.07.002

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Keywords

  • Monoterpene indole alkaloids
  • Vallesiachotamine
  • Catechol-O-methyltransferase
  • Docking
  • Neurodegenerative diseases