No / The indoloquinoline alkaloid cryptolepine 1 has potent in vitro antiplasmodial activity, but it is also a DNA intercalator with cytotoxic properties. We have shown that the antiplasmodial mechanism of 1 is likely to be due, at least in part, to a chloroquine-like action that does not depend on intercalation into DNA. A number of substituted analogues of 1 have been prepared that have potent activities against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum and also have in common with chloroquine the inhibition of ß-hematin formation in a cell-free system. Several compounds also displayed activity against Plasmodium berghei in mice, the most potent being 2,7-dibromocryptolepine 8, which suppressed parasitemia by 89% as compared to untreated infected controls at a dose of 12.5 mg kg-1 day-1 ip. No correlation was observed between in vitro cytotoxicity and the effect of compounds on the melting point of DNA (¿Tm value) or toxicity in the mouse¿malaria model.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/3946 |
| Date | January 2001 |
| Creators | Wright, Colin W., Addae-Kyereme, Jonathan A., Breen, Anthony G., Brown, John E., Cox, Marlene F., Croft, S.L., Gokcek, Yaman, Kendrick, H., Phillips, Roger M., Pollet, Pamela L. |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, No full-text available in the repository |
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