Antimalarial Activity of Crambescidin 800 and Synthetic Analogues against Liver and Blood Stage of Plasmodium sp
Structural features associated with the antimalarial activity of the marine natural product crambescidin 800 were studied using synthetic analogues of the related compound ptilomycalin A. The study suggests that the guanidine moiety is cytotoxic, whereas the spermidine-containing aliphatic chain inc...
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Veröffentlicht in: | Journal of antibiotics 2006-09, Vol.59 (9), p.583-590 |
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Hauptverfasser: | , , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Structural features associated with the antimalarial activity of the marine natural product crambescidin 800 were studied using synthetic analogues of the related compound ptilomycalin A. The study suggests that the guanidine moiety is cytotoxic, whereas the spermidine-containing aliphatic chain increases activity. The most active analogue, compound
11
, had
in vitro
activity against
Plasmodium falciparum
strain 3D7 (IC
50
=490 nM) that was stronger than the
in vitro
activity against murine L5178Y cells (IC
50
=8.5~59 μM).
In vitro
growth inhibition of liver stages of
P. yoelii yoelii
in mouse hepatocytes was observed (IC
50
=9.2 μM). The compound did not significantly prolong median survival time after a single subcutaneous administration of 80 mg/kg in
P. berghei
-infected mice. Compound
11
did not cause DNA fragmentation in an
in vitro
micronucleus assay. |
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ISSN: | 0021-8820 1881-1469 |
DOI: | 10.1038/ja.2006.78 |