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1. Fitoterapia. 2012 Mar 17. [Epub ahead of print]

Mechanism-based CYP2D6 inactivation by acridone alkaloids of Indonesian medicinal
plant Lunasia amara.

Takahashi N, Lallo S, Kadota S, Tezuka Y.

Fourteen acridone alkaloids isolated from Lunasia amara Blanco were tested for
their mechanism-based inhibition on human liver microsomal dextromethorphan
O-demethylation activity, a prototype marker for cytochrome P450 2D6 (CYP2D6).
Among the 14 compounds, 5-hydroxygraveroline (1), 8-methoxyifflaiamine (2),
lunamarine (3), and lunine (12) increased their inhibitory activity with
increasing preincubation time. Then, we further examined the possibility of
mechanism-based inhibition on 5-hydroxygraveroline (1) and lunamarine (3), which
showed the potent inhibition. Further investigations on 1 and 3 showed that the
characteristic time- and concentration-dependent inhibition, which required a
catalytic step with NADPH, was not protected by nucleophiles, and was decreased
by the presence of a competitive inhibitor. Thus, 1 and 3 were concluded as
mechanism-based inactivators of CYP2D6.

Copyright © 2012. Published by Elsevier B.V.

PMID: 22465502 [PubMed - as supplied by publisher]