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Allylpolyalkoxybenzene Inhibitors of Galactonolactone Oxidase from Trypanosoma cruzi

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Abstract

Inhibition of biosynthetic pathways of compounds essential for Trypanosoma cruzi is considered as one of the possible action mechanisms of drugs against Chagas disease. Here, we investigated the inhibition of galactonolactone oxidase from T. cruzi (TcGAL), which catalyzes the final step in the synthesis of vitamin C, an antioxidant that T. cruzi is unable to assimilate from outside and must synthesize itself, and identified allylbenzenes from plant sources as a new class of TcGAL inhibitors. Natural APABs (apiol, dillapiol, etc.) inhibited TcGAL with IC50 = 20-130 µM. The non-competitive mechanism of TcGAL inhibition by apiol was established. Conjugation of APABs with triphenylphosphonium, which ensures selective delivery of biologically active substances to the mitochondria, increased the efficiency and/or the maximum percentage of TcGAL inhibition compared to nonmodified APABs.

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Abbreviations

AOT:

sodium bis(2-ethylhexyl) sulfosuccinate

APAB:

allylpolyalkoxybenzene

ATMB:

allyltetramethoxybenzene

TcGAL:

galactonolactone oxidase from Trypanosoma cruzi

TPP:

triphenylphosphonium

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Acknowledgments

This work was performed using equipment (FTIR spectrometer Bruker Tensor 27 and Jasco J-815 CD Spectrometer) of the program for the development of Moscow State University.

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Authors and Affiliations

  1. Faculty of Chemistry, Lomonosov Moscow State University, 119991, Moscow, Russia

    Andrey A. Chudin, Igor D. Zlotnikov & Elena V. Kudryashova

  2. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991, Moscow, Russia

    Sergey S. Krylov & Victor V. Semenov

Authors
  1. Andrey A. Chudin
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  2. Igor D. Zlotnikov
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  3. Sergey S. Krylov
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  4. Victor V. Semenov
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  5. Elena V. Kudryashova
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Contributions

E.V.K. conceptualized and supervised the study; V.V.S. and S.S.K. developed the strategy for studying inhibitor series; A.A.Ch. conducted the experiments and wrote the article; I.D.Z. recorded and analyzed FTIR spectra; E.V.K., A.A.Ch., V.V.S., and S.S.K. discussed the results; E.V.K., A.A.Ch., and V.V.S. edited the manuscript.

Corresponding author

Correspondence to Elena V. Kudryashova.

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The authors declare no conflict of interest. This article contains no description of studies using humans or animals performed by any of the authors.

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Chudin, A.A., Zlotnikov, I.D., Krylov, S.S. et al. Allylpolyalkoxybenzene Inhibitors of Galactonolactone Oxidase from Trypanosoma cruzi. Biochemistry Moscow 88, 131–141 (2023). https://doi.org/10.1134/S000629792301011X

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