Wright, C.W., Addee-Kyereme, J., Breen, A.G., Brown, J.E., Cox, M.F., Croft, S.L., Gokcek, Y., Kendrick, H., Phillips, Roger M. and Pollet, P.L. (2001) Synthesis and evaluation of cryptolepine analogues for their potential as new antimalarial agents. Journal of Medicinal Chemistry, 44 (19). pp. 3187-3194. ISSN 0022-2623Metadata only available from this repository.
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 beta-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 (DeltaT(m) value) or toxicity in the mouse-malaria model.
|Subjects:||R Medicine > RM Therapeutics. Pharmacology|
|Schools:||School of Applied Sciences|
|Depositing User:||Roger Phillips|
|Date Deposited:||14 May 2015 09:10|
|Last Modified:||14 May 2015 09:10|
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