@article{fdi:010069389,
  title = {{R}ole of quinone reductase 2 in the antimalarial properties of indolone-type derivatives},
  author = {{C}assagnes, {L}. {E}. and {R}akotoarivelo, {N}. and {S}irigu, {S}. and {P}erio, {P}ierre and {N}ajahi, {E}. and {C}havas, {L}. {M}. {G}. and {T}hompson, {A}. and {G}ayon, {R}. and {F}erry, {G}. and {B}outin, {J}. {A}. and {V}alentin, {A}. and {R}eybier, {K}. and {N}epveu, {F}.},
  editor = {},
  language = {{ENG}},
  abstract = {{I}ndolone-{N}-oxides have antiplasmodial properties against {P}lasmodium falciparum at the erythrocytic stage, with {IC}50 values in the nanomolar range. {T}he mechanism of action of indolone derivatives involves the production of free radicals, which follows their bioreduction by an unknown mechanism. {I}n this study, we hypothesized that human quinone reductase 2 (h{QR}2), known to act as a flavin redox switch upon binding to the broadly used antimalarial chloroquine, could be involved in the activity of the redox-active indolone derivatives. {T}herefore, we investigated the role of h{QR}2 in the reduction of indolone derivatives. {W}e analyzed the interaction between h{QR}2 and several indolone-type derivatives by examining enzymatic kinetics, the substrate/protein complex structure with {X}-ray diffraction analysis, and the production of free radicals with electron paramagnetic resonance. {T}he reduction of each compound in cells overexpressing h{QR}2 was compared to its reduction in naive cells. {T}his process could be inhibited by the specific h{QR}2 inhibitor, {S}29434. {T}hese results confirmed that the anti-malarial activity of indolone-type derivatives was linked to their ability to serve as h{QR}2 substrates and not as h{QR}2 inhibitors as reported for chloroquine, leading to the possibility that substrate of h{QR}2 could be considered as a new avenue for the design of new antimalarial compounds.},
  keywords = {malaria ; inhibitor ; mechanism ; human quinone reductase 2 ; indolones},
  booktitle = {},
  journal = {{M}olecules},
  volume = {22},
  numero = {2},
  pages = {art. 210 [16 p.]},
  ISSN = {1420-3049},
  year = {2017},
  DOI = {10.3390/molecules22020210},
  URL = {https://www.documentation.ird.fr/hor/fdi:010069389},
}