Allylpolyalkoxybenzene Inhibitors of Galactonolactone Oxidase from Trypanosoma cruzi

Allylpolyalkoxybenzene Inhibitors of Galactonolactone Oxidase from Trypanosoma cruzi Full article

Journal

Biochemistry-Moscow
ISSN: 0006-2979 , E-ISSN: 1608-3040

Output data

Year: 2023, Volume: 88, Number: 1, Pages: 131-141 Pages count : 11 DOI: 10.1134/s000629792301011x

Authors

Chudin Andrey A. ¹ , Zlotnikov Igor D. ¹ , Krylov Sergey S. ² , Semenov Victor V. ² , Kudryashova Elena V. ¹

Affiliations

1	Faculty of Chemistry, Lomonosov Moscow State University, 119991, Moscow, Russia
2	Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991, Moscow, Russia

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.

Chudin A.A. , Zlotnikov I.D. , Krylov S.S. , Semenov V.V. , Kudryashova E.V.
Allylpolyalkoxybenzene Inhibitors of Galactonolactone Oxidase from Trypanosoma cruzi
Biochemistry-Moscow. 2023. V.88. N1. P.131-141. DOI: 10.1134/s000629792301011x WOS Scopus OpenAlex

Web of science:	WOS:000936418100011
Scopus:	2-s2.0-85148375627
OpenAlex:	W4321199954

DB	Citing
OpenAlex	9
Scopus	9
Web of science	8