Pro-oxidant properties of indolone-N-oxides in relation to their antimalarial properties
Identifieur interne : 000188 ( France/Analysis ); précédent : 000187; suivant : 000189Pro-oxidant properties of indolone-N-oxides in relation to their antimalarial properties
Auteurs : Thi Hoang Yen Nguyen [Viêt Nam] ; Hany Ibrahim [France] ; Karine Reybier [France] ; Pierre Perio [France] ; Florence Souard [France] ; Ennaji Najahi [France] ; Paul-Louis Fabre [France] ; Françoise Nepveu [France]Source :
- Journal of Inorganic Biochemistry [ 0162-0134 ] ; 2013.
Abstract
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.
Url:
DOI: 10.1016/j.jinorgbio.2013.04.012
Affiliations:
Links toward previous steps (curation, corpus...)
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Hal:hal-00875563Le document en format XML
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<orgName>Centre National de la Recherche Scientifique</orgName>
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<date type="start">1939-10-19</date>
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<country>France</country>
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<idno type="DOI">10.1016/j.jinorgbio.2013.04.012</idno>
<series><title level="j">Journal of Inorganic Biochemistry</title>
<idno type="ISSN">0162-0134</idno>
<imprint><date type="datePub">2013</date>
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<profileDesc><textClass><keywords scheme="mix" xml:lang="es"><term>Antimalarial drugs</term>
<term>Cyclic voltammetry</term>
<term>Electron paramagnetic resonance (EPR)</term>
<term>Indolone-N-oxides</term>
<term>Pro-oxidant drugs</term>
</keywords>
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<front><div type="abstract" xml:lang="en"> <p>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.</p>
</div>
</front>
</TEI>
<affiliations><list><country><li>France</li>
<li>Viêt Nam</li>
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<tree><country name="Viêt Nam"><noRegion><name sortKey="Nguyen, Thi Hoang Yen" sort="Nguyen, Thi Hoang Yen" uniqKey="Nguyen T" first="Thi Hoang Yen" last="Nguyen">Thi Hoang Yen Nguyen</name>
</noRegion>
</country>
<country name="France"><noRegion><name sortKey="Ibrahim, Hany" sort="Ibrahim, Hany" uniqKey="Ibrahim H" first="Hany" last="Ibrahim">Hany Ibrahim</name>
</noRegion>
<name sortKey="Fabre, Paul Louis" sort="Fabre, Paul Louis" uniqKey="Fabre P" first="Paul-Louis" last="Fabre">Paul-Louis Fabre</name>
<name sortKey="Najahi, Ennaji" sort="Najahi, Ennaji" uniqKey="Najahi E" first="Ennaji" last="Najahi">Ennaji Najahi</name>
<name sortKey="Nepveu, Francoise" sort="Nepveu, Francoise" uniqKey="Nepveu F" first="Françoise" last="Nepveu">Françoise Nepveu</name>
<name sortKey="Perio, Pierre" sort="Perio, Pierre" uniqKey="Perio P" first="Pierre" last="Perio">Pierre Perio</name>
<name sortKey="Reybier, Karine" sort="Reybier, Karine" uniqKey="Reybier K" first="Karine" last="Reybier">Karine Reybier</name>
<name sortKey="Souard, Florence" sort="Souard, Florence" uniqKey="Souard F" first="Florence" last="Souard">Florence Souard</name>
</country>
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</affiliations>
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