OATAO - Open Archive Toulouse Archive Ouverte Open Access Week

Pro-oxidant properties of indolone-N-oxides in relation to their antimalarial properties

Nguyen, Thi Hoang Yen and Ibrahim, Hany and Reybier, Karine and Perio, Pierre and Souard, Florence and Najahi, Ennaji and Fabre, Paul-Louis and Nepveu, Françoise Pro-oxidant properties of indolone-N-oxides in relation to their antimalarial properties. (2013) Journal of Inorganic Biochemistry, 126. 7-16. ISSN 0162-0134

(Document in English)

PDF (Author's version) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader

Official URL: http://dx.doi.org/10.1016/j.jinorgbio.2013.04.012


Indolone-N-oxides (INODs) are bioreducible and possess remarkable anti-malarial activities in the low nanomolar range in vitro against different Plasmodium falciparum (P. falciparum) strains and in vivo. INODs have an original mechanism of action: they damage the host cell membrane without affecting non-parasitized erythrocytes. These molecules produce a redox signal which activates SYK tyrosine kinases and induces a hyperphosphorylation of AE1 (band 3, erythrocyte membrane protein). The present work aimed to understand the early stages of the biochemical interactions of these compounds with some erythrocyte components from which the redox signal could originate. The interactions were studied in a biomimetic model and compared with those of chloroquine and artemisinin. The results showed that INODs i) do not enter the coordination sphere of the metal in the heme iron complex as does chloroquine; ii) do not generate iron-dependent radicals as does artemisinin; iii) generate stable free radical adducts after reduction at one electron; iv) cannot trap free radicals after reduction. These results confirm that the bioactivity of INODs does not lie in their spin-trapping properties but rather in their pro-oxidant character. This property may be the initiator of the redox signal which activates SYK tyrosine kinases.

Item Type:Article
Additional Information:Thanks to Elsevier editor. The definitive version is avaialable at http://www.sciencedirect.com The original PDF can be found at Journal of Inorganic Biochemistry website: http://www.sciencedirect.com/science/article/pii/S0162013413001037
HAL Id:hal-00875563
Audience (journal):International peer-reviewed journal
Uncontrolled Keywords:
Institution:French research institutions > Centre National de la Recherche Scientifique - CNRS (FRANCE)
Université de Toulouse > Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE)
French research institutions > Institut de Recherche pour le Développement - IRD (FRANCE)
Université de Toulouse > Université Toulouse III - Paul Sabatier - UT3 (FRANCE)
Other partners > University of Medicine and Pharmacy (VIETNAM)
Laboratory name:
Deposited On:22 Oct 2013 10:20

Repository Staff Only: item control page