Interaction of Artemisinins with Oxyhemoglobin Hb–FeII, Hb–FeII, CarboxyHb–FeII, Heme–FeII, and Carboxyheme FeII: Significance for Mode of Action and Implications for Therapy of Cerebral Malaria
Identifieur interne : 001860 ( Main/Exploration ); précédent : 001859; suivant : 001861Interaction of Artemisinins with Oxyhemoglobin Hb–FeII, Hb–FeII, CarboxyHb–FeII, Heme–FeII, and Carboxyheme FeII: Significance for Mode of Action and Implications for Therapy of Cerebral Malaria
Auteurs : Paolo Coghi ; Nicoletta Basilico [Italie] ; Donatella Taramelli [Italie] ; Wing-Chi Chan ; Richard Haynes [Hong Kong] ; Diego Monti [Italie]Source :
- ChemMedChem [ 1860-7179 ] ; 2009-12-07.
English descriptors
- Teeft :
- Absorption spectra, Absorption spectrum, Agents chemother, Alkylation, Angew, Antimalarial, Antimalarial activities, Antimalarial activity, Aqueous buffer, Artemisinin, Artemisinins, Artemisone, Artesunate, Biochem, Cerebral malaria, Ch3cn, Ch3cn buffer, Chem, Chemmedchem, Derivative, Dithionite, Dmso, Dmso buffer, Falciparum parasites, Feii, Ferrous, Ferrous heme, Ferrous iron, Gmbh, Haynes, Heme, Human hemoglobin, Kgaa, Lmax, Meunier, Monti, Parasite, Same procedure, Sodium dithionite, Soret band, Standard microaerophilic conditions, Verlag, Verlag gmbh, Weinheim, Weinheim chemmedchem.
Abstract
In line with the enhancement of antimalarial activities of the current clinical artemisinins against parasites cultured under CO, the artemisinins are unaffected in vitro by carboxyhemoglobin (CO–Hb–FeII) or CO–heme–FeII, but are competitively decomposed by Hb–FeII or heme–FeII. In the latter case, the heme studies are greatly facilitated by solubilization of the heme in aqueous medium by use of arginine. None of the Hb species has an appreciable effect on artemisone, or on other aminoartemisinins, and antimalarial activities are either less affected or remain essentially unchanged against parasites cultured under standard microaerophilic conditions or under CO. The findings not only indicate that artemisinins do not require Hb–FeII or heme–FeII for promotion of antimalarial activity, but are also important in relation to the therapy of severe/complicated or cerebral malaria.
The antimalarial activities of Hb–FeII and heme–FeII‐susceptible artemisinins against parasites cultured under CO are substantially increased with respect to parasites cultured under microaerophilic conditions, in accord with observed inertness to CO–Hb–FeII and CO–heme–FeII. Aminoartemisinins display similar activities toward parasites cultured under these separate conditions, in line with their relative inertness to all heme species under biological conditions.
Url:
DOI: 10.1002/cmdc.200900342
Affiliations:
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Diego" uniqKey="Monti D" first="Diego" last="Monti">Diego Monti</name><affiliation></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Italie</country></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">ChemMedChem</title><title level="j" type="alt">CHEMMEDCHEM</title><idno type="ISSN">1860-7179</idno><idno type="eISSN">1860-7187</idno><imprint><biblScope unit="vol">4</biblScope><biblScope unit="issue">12</biblScope><biblScope unit="page" from="2045">2045</biblScope><biblScope unit="page" to="2053">2053</biblScope><biblScope unit="page-count">9</biblScope><publisher>WILEY‐VCH Verlag</publisher><pubPlace>Weinheim</pubPlace><date type="published" when="2009-12-07">2009-12-07</date></imprint><idno type="ISSN">1860-7179</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1860-7179</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Absorption spectra</term><term>Absorption spectrum</term><term>Agents chemother</term><term>Alkylation</term><term>Angew</term><term>Antimalarial</term><term>Antimalarial activities</term><term>Antimalarial activity</term><term>Aqueous buffer</term><term>Artemisinin</term><term>Artemisinins</term><term>Artemisone</term><term>Artesunate</term><term>Biochem</term><term>Cerebral malaria</term><term>Ch3cn</term><term>Ch3cn buffer</term><term>Chem</term><term>Chemmedchem</term><term>Derivative</term><term>Dithionite</term><term>Dmso</term><term>Dmso buffer</term><term>Falciparum parasites</term><term>Feii</term><term>Ferrous</term><term>Ferrous heme</term><term>Ferrous iron</term><term>Gmbh</term><term>Haynes</term><term>Heme</term><term>Human hemoglobin</term><term>Kgaa</term><term>Lmax</term><term>Meunier</term><term>Monti</term><term>Parasite</term><term>Same procedure</term><term>Sodium dithionite</term><term>Soret band</term><term>Standard microaerophilic conditions</term><term>Verlag</term><term>Verlag gmbh</term><term>Weinheim</term><term>Weinheim chemmedchem</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In line with the enhancement of antimalarial activities of the current clinical artemisinins against parasites cultured under CO, the artemisinins are unaffected in vitro by carboxyhemoglobin (CO–Hb–FeII) or CO–heme–FeII, but are competitively decomposed by Hb–FeII or heme–FeII. In the latter case, the heme studies are greatly facilitated by solubilization of the heme in aqueous medium by use of arginine. None of the Hb species has an appreciable effect on artemisone, or on other aminoartemisinins, and antimalarial activities are either less affected or remain essentially unchanged against parasites cultured under standard microaerophilic conditions or under CO. The findings not only indicate that artemisinins do not require Hb–FeII or heme–FeII for promotion of antimalarial activity, but are also important in relation to the therapy of severe/complicated or cerebral malaria.</div><div type="abstract" xml:lang="en">The antimalarial activities of Hb–FeII and heme–FeII‐susceptible artemisinins against parasites cultured under CO are substantially increased with respect to parasites cultured under microaerophilic conditions, in accord with observed inertness to CO–Hb–FeII and CO–heme–FeII. Aminoartemisinins display similar activities toward parasites cultured under these separate conditions, in line with their relative inertness to all heme species under biological conditions.</div></front></TEI><affiliations><list><country><li>Hong Kong</li><li>Italie</li></country></list><tree><noCountry><name sortKey="Chan, Wing Hi" sort="Chan, Wing Hi" uniqKey="Chan W" first="Wing-Chi" last="Chan">Wing-Chi Chan</name><name sortKey="Coghi, Paolo" sort="Coghi, Paolo" uniqKey="Coghi P" first="Paolo" last="Coghi">Paolo Coghi</name></noCountry><country name="Italie"><noRegion><name sortKey="Basilico, Nicoletta" sort="Basilico, Nicoletta" uniqKey="Basilico N" first="Nicoletta" last="Basilico">Nicoletta Basilico</name></noRegion><name sortKey="Monti, Diego" sort="Monti, Diego" uniqKey="Monti D" first="Diego" last="Monti">Diego Monti</name><name sortKey="Taramelli, Donatella" sort="Taramelli, Donatella" uniqKey="Taramelli D" first="Donatella" last="Taramelli">Donatella Taramelli</name></country><country name="Hong Kong"><noRegion><name sortKey="Haynes, Richard" sort="Haynes, Richard" uniqKey="Haynes R" first="Richard" last="Haynes">Richard Haynes</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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