Allylpolyalkoxybenzene Inhibitors of Galactonolactone Oxidase from Trypanosoma cruzi

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 synth...

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Bibliographic Details
Published in:Biochemistry (Moscow) 2023, Vol.88 (1), p.131-141
Main Authors: Chudin, Andrey A., Zlotnikov, Igor D., Krylov, Sergey S., Semenov, Victor V., Kudryashova, Elena V.
Format: Article
Language:English
Subjects:
Analysis
Ascorbic acid
Biochemistry
Biological activity
Biomedical and Life Sciences
Biomedicine
Bioorganic Chemistry
Biosynthesis
Care and treatment
Chagas Disease
Conjugation
Enzymes
Humans
Identification and classification
Inhibitors
Life Sciences
Metabolites
Microbiology
Mitochondria
Organic chemistry
Oxidase
Oxidases
Oxidoreductases - metabolism
Parasites
Properties
Protozoa
Sodium
Sterols
Sugar Acids - metabolism
Trypanosoma cruzi
Trypanosoma cruzi - metabolism
Vector-borne diseases
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Summary: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 IC 50 = 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.
ISSN:0006-2979
1608-3040
DOI:10.1134/S000629792301011X