Inhibitors of galactonolactone oxidase from Trypanosoma cruzi based on allylpolyalkoxybenzenes

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Дәйексөз келтіру

Толық мәтін

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Рұқсат жабық Тек жазылушылар үшін

Аннотация

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.

Авторлар туралы

A. Chudin

Faculty of Chemistry, Lomonosov Moscow State University

Email: helenakoudriachova@yandex.ru
119991 Moscow, Russia

I. Zlotnikov

Faculty of Chemistry, Lomonosov Moscow State University

Email: helenakoudriachova@yandex.ru
119991 Moscow, Russia

S. Krylov

N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences

Email: helenakoudriachova@yandex.ru
119991 Moscow, Russia

V. Semenov

N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences

Email: helenakoudriachova@yandex.ru
119991 Moscow, Russia

E. Kudryashova

Faculty of Chemistry, Lomonosov Moscow State University

Email: helenakoudriachova@yandex.ru
119991 Moscow, Russia

Әдебиет тізімі

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© Russian Academy of Sciences, 2023

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