1. Studies on aldose reductase inhibitors from fungi. I. Citrinin and related benzopyran derivatives.
- Author
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Deruiter J, Jacyno JM, Davis RA, and Cutler HG
- Subjects
- Animals, Eye enzymology, Fungi metabolism, Kinetics, Penicillium chemistry, Rats, Structure-Activity Relationship, Aldehyde Reductase antagonists & inhibitors, Benzopyrans pharmacology, Citrinin analogs & derivatives, Citrinin pharmacology
- Abstract
The fungal metabolites, citrinin (4,6-dihydro-8-hydroxy-3,4,5-trimethyl-6- oxo-3H-2-benzopyran-7-carboxylic acid) and DHMI (3,4-dihydro-6-methoxy-3,7-dimethyl-1H-2-benzopyran-8-ol), as well as certain synthetic derivatives, have been evaluated for aldose reductase inhibitory activity using a rat lens enzyme preparation. Citrinin and its reduction product, dihydrocitrinin, were found to have significant activity (IC50 approximately 10 microM), whereas the other compounds were 3-10 times less potent. Kinetic studies showed that citrinin was not an irreversible inhibitor of the enzyme, as might be expected of a quinone methide. Spectroscopic (NMR) evidence is presented for the existence of citrinin predominantly in the form of its hemi-acetal in aqueous solutions, suggesting that it is this benzo[c]pyran derivative which interacts with the enzyme, rather than the quinone methide form.
- Published
- 1992
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