Targeting the Erythrocytic and Liver Stages of Malaria Parasites with s‐Triazine‐Based Hybrids
Identifieur interne : 000F20 ( Main/Exploration ); précédent : 000F19; suivant : 000F21Targeting the Erythrocytic and Liver Stages of Malaria Parasites with s‐Triazine‐Based Hybrids
Auteurs : Catarina A. B. Rodrigues [Portugal] ; Raquel F. M. Frade [Portugal] ; Inês S. Albuquerque [Portugal] ; Maria J. Perry [Portugal] ; Jiri Gut [États-Unis] ; Marta Machado [Portugal] ; Philip J. Rosenthal [États-Unis] ; Miguel Prudêncio [Portugal] ; Carlos A. M. Afonso [Portugal] ; Rui Moreira [Portugal]Source :
- ChemMedChem [ 1860-7179 ] ; 2015-05.
Abstract
A diversity‐oriented library of s‐triazine‐based hybrids was screened for activity against the chloroquine‐resistant Plasmodium falciparum W2 strain. The most striking result was sub‐micromolar activity against cultured erythrocytic‐stage parasites of hybrid molecules containing one or two 8‐aminoquinoline moieties. These compounds were not clearly toxic to human cells. The most effective blood‐schizontocidal s‐triazine derivatives were then screened for activity against the liver stage of malaria parasites. The s‐triazine hybrid containing two 8‐aminoquinoline moieties and one chlorine atom emerged as the most potent against P. berghei liver‐stage infection, active in the low nanomolar region, combined with good metabolic stability in rat liver microsomes. These results indicate that s‐triazine‐8‐aminoquinoline‐based hybrids are excellent starting points for lead optimization as dual‐stage antimalarials.
Double‐edged sword to kill malaria parasites: s‐Triazine‐based hybrid compounds containing a primaquine moiety were found to be dual‐stage antiplasmodial agents. The two hybrids are highly potent against both the liver and blood stages of the parasite's life cycle and show excellent metabolic stability.
Url:
DOI: 10.1002/cmdc.201500011
Affiliations:
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Prof. Gama Pinto</wicri:noRegion></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">10</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="883">883</biblScope><biblScope unit="page" to="890">890</biblScope><biblScope unit="page-count">8</biblScope><publisher>WILEY‐VCH Verlag</publisher><pubPlace>Weinheim</pubPlace><date type="published" when="2015-05">2015-05</date></imprint><idno type="ISSN">1860-7179</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1860-7179</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">A diversity‐oriented library of s‐triazine‐based hybrids was screened for activity against the chloroquine‐resistant Plasmodium falciparum W2 strain. The most striking result was sub‐micromolar activity against cultured erythrocytic‐stage parasites of hybrid molecules containing one or two 8‐aminoquinoline moieties. These compounds were not clearly toxic to human cells. The most effective blood‐schizontocidal s‐triazine derivatives were then screened for activity against the liver stage of malaria parasites. The s‐triazine hybrid containing two 8‐aminoquinoline moieties and one chlorine atom emerged as the most potent against P. berghei liver‐stage infection, active in the low nanomolar region, combined with good metabolic stability in rat liver microsomes. These results indicate that s‐triazine‐8‐aminoquinoline‐based hybrids are excellent starting points for lead optimization as dual‐stage antimalarials.</div><div type="abstract" xml:lang="en">Double‐edged sword to kill malaria parasites: s‐Triazine‐based hybrid compounds containing a primaquine moiety were found to be dual‐stage antiplasmodial agents. The two hybrids are highly potent against both the liver and blood stages of the parasite's life cycle and show excellent metabolic stability.</div></front></TEI><affiliations><list><country><li>Portugal</li><li>États-Unis</li></country><region><li>Californie</li></region></list><tree><country name="Portugal"><noRegion><name sortKey="Rodrigues, Catarina A B" sort="Rodrigues, Catarina A B" uniqKey="Rodrigues C" first="Catarina A. B." last="Rodrigues">Catarina A. B. Rodrigues</name></noRegion><name sortKey="Afonso, Carlos A M" sort="Afonso, Carlos A M" uniqKey="Afonso C" first="Carlos A. M." last="Afonso">Carlos A. M. Afonso</name><name sortKey="Afonso, Carlos A M" sort="Afonso, Carlos A M" uniqKey="Afonso C" first="Carlos A. M." last="Afonso">Carlos A. M. Afonso</name><name sortKey="Afonso, Carlos A M" sort="Afonso, Carlos A M" uniqKey="Afonso C" first="Carlos A. M." last="Afonso">Carlos A. M. Afonso</name><name sortKey="Albuquerque, Ines S" sort="Albuquerque, Ines S" uniqKey="Albuquerque I" first="Inês S." last="Albuquerque">Inês S. Albuquerque</name><name sortKey="Frade, Raquel F M" sort="Frade, Raquel F M" uniqKey="Frade R" first="Raquel F. M." last="Frade">Raquel F. M. Frade</name><name sortKey="Machado, Marta" sort="Machado, Marta" uniqKey="Machado M" first="Marta" last="Machado">Marta Machado</name><name sortKey="Moreira, Rui" sort="Moreira, Rui" uniqKey="Moreira R" first="Rui" last="Moreira">Rui Moreira</name><name sortKey="Moreira, Rui" sort="Moreira, Rui" uniqKey="Moreira R" first="Rui" last="Moreira">Rui Moreira</name><name sortKey="Moreira, Rui" sort="Moreira, Rui" uniqKey="Moreira R" first="Rui" last="Moreira">Rui Moreira</name><name sortKey="Perry, Maria J" sort="Perry, Maria J" uniqKey="Perry M" first="Maria J." last="Perry">Maria J. Perry</name><name sortKey="Prudencio, Miguel" sort="Prudencio, Miguel" uniqKey="Prudencio M" first="Miguel" last="Prudêncio">Miguel Prudêncio</name></country><country name="États-Unis"><region name="Californie"><name sortKey="Gut, Jiri" sort="Gut, Jiri" uniqKey="Gut J" first="Jiri" last="Gut">Jiri Gut</name></region><name sortKey="Rosenthal, Philip J" sort="Rosenthal, Philip J" uniqKey="Rosenthal P" first="Philip J." last="Rosenthal">Philip J. Rosenthal</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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