Structure–activity relationships of ganoderma acids from Ganoderma lucidum as aldose reductase inhibitors

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Abstract

A series of lanostane-type triterpenoids, known as ganoderma acids were isolated from the fruiting body of Ganoderma lucidum. Some of these compounds were identified as active inhibitors of the in vitro human recombinant aldose reductase. To clarify the structural requirement for inhibition, some structure–activity relationships were determined. Our structure–activity studies of ganoderma acids revealed that the OH substituent at C-11 is an important feature and the carboxylic group in the side chain is essential for the recognition of aldose reductase inhibitory activity. Moreover, double bond moiety at C-20 and C-22 in the side chain contributes to improving aldose reductase inhibitory activity. In the case of ganoderic acid C2, all of OH substituent at C-3, C-7 and C-15 is important for potent aldose reductase inhibition. These results provide an approach to understanding the structural requirements of ganoderma acids from G. lucidum for aldose reductase inhibitor. This understanding is necessary to design a new-type of aldose reductase inhibitor.

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Acknowledgements

We are thankful to Dr. Miyamoto for optical rotation measurement, to Mr. Matsumoto for HRESIMS measurement and Hitachi Scholarship Foundation - Japan, for postgraduate scholarship to S.F. The costs of publication were supported in part by the Research Grant for Young Investigators of Faculty of Agriculture, Kyushu University.

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