Email this article Inhibitors of galactonolactone oxidase from Trypanosoma cruzi based on allylpolyalkoxybenzenes
- Authors: Chudin A.A1, Zlotnikov I.D1, Krylov S.S2, Semenov V.V2, Kudryashova E.V1
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Affiliations:
- Faculty of Chemistry, Lomonosov Moscow State University
- N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences
- Issue: Vol 88, No 1 (2023)
- Pages: 97-109
- Section: Articles
- URL: https://journals.rcsi.science/0320-9725/article/view/144628
- DOI: https://doi.org/10.31857/S0320972523010074
- EDN: https://elibrary.ru/PCFZWJ
- ID: 144628
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Abstract
Inhibition of the biosynthetic pathways of compounds essential for T. cruzi is considered by researchers as one of the possible mechanisms of action of potential drugs against Chagas disease. As one of these mechanisms, we consider 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. In this work, for the first time, a class of effective inhibitors of TcGAL was found - allylbenzenes from plant sources. A non-competitive mechanism of action of apiol has been established and it has been found that natural allylpolyalkoxybenzenes (APAB) - apiol, dillapiol, etc. are effective inhibitors of TcGAL with IC50 = 20-130 µM. It was found that the conjugation of APAB with triphenylphosphonium, which ensures the selective delivery of biologically active substances to mitochondria, makes it possible to increase the efficiency and/or the maximum percentage of inhibition compared to unmodified APAB.
About the authors
A. A Chudin
Faculty of Chemistry, Lomonosov Moscow State University
Email: helenakoudriachova@yandex.ru
119991 Moscow, Russia
I. D Zlotnikov
Faculty of Chemistry, Lomonosov Moscow State University
Email: helenakoudriachova@yandex.ru
119991 Moscow, Russia
S. S Krylov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences
Email: helenakoudriachova@yandex.ru
119991 Moscow, Russia
V. V Semenov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences
Email: helenakoudriachova@yandex.ru
119991 Moscow, Russia
E. V Kudryashova
Faculty of Chemistry, Lomonosov Moscow State University
Email: helenakoudriachova@yandex.ru
119991 Moscow, Russia
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