No / Objectives To investigate the metabolism of cryptolepine and some cryptolepine
analogues by aldehyde oxidase, and to assess the implications of the results on the
potential of cryptolepine analogues as antimalarial agents.
Methods The products resulting from the oxidation of cryptolepine and
2-fluorocryptolepine by a rabbit liver preparation of aldehyde oxidase were isolated
and identified using chromatographic and spectroscopic techniques. The antiplasmodial
activity of cryptolepine-11-one was assessed against Plasmodium falciparum
using the parasite lactate dehydrogenase assay.
Key findings Cryptolepine was oxidized by aldehyde oxidase give cryptolepine-11-
one. Although 2-fluorocryptolepine was found to have less affinity for the enzyme
than cryptolepine,it was a better substrate for aldehyde oxidase than the parent compound.
In contrast, quindoline, the 11-chloro- , 2,7-dibromo- and 2-methoxy analogues
of cryptolepine were not readily oxidized. Cryptolepine-11-one was found to
be inactive against P. falciparum in vitro raising the possibility that the effectiveness
of cryptolepine as an antimalarial, may be compromised by metabolism to an
inactive metabolite by liver aldehyde oxidase.
Conclusions Cryptolepine and 2-fluorocryptolepine are substrates for aldehyde
oxidase. This may have implications for the design and development of cryptolepine
analogues as antimalarial agents.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/7466 |
| Date | January 2012 |
| Creators | Stell, J. Godfrey P., Wheelhouse, Richard T., Wright, Colin W. |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, No full-text in the repository |
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