ANTIMUTAGENIC ACTIVITY OF ISOFRAXINELLONE FROM DICTAMNUS-DASYCARPUS

A dichloromethane extract from Dictamnus dasycarpus showed a suppressive effect on umu gene expression of the SOS response in Salmonella typhimurium TA1535/pSK1002 against the mutagen 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (furylfuramide). The suppressive compound in the dichloromethane extract from D. dasycarpus was isolated by SiO2 column chromatography and identified as isofraxinellone by EI-MS and H-1 and C-13 NMR spectroscopy. Isofraxinellone exhibited an inhibition of the SOS-inducing activity of furylfuramide in the umu test. Gene expression was suppressed completely at less than 0.86 mu mol/mL, and the ID50 value was 0.35 mu mol/mL. Fraxinellone, which was one of the major components in D. dasycarpus, was also isolated, but this compound did not show any suppressive effect on the SOS induction of furylfuramide. Isofraxinellone was also assayed with the mutagen 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-l), which requires liver metabolizing enzymes, and showed a suppressive effect similar to that with furylfuramide. Its ID50 value against Trp-P-l was 0.50 mu mol/mL. The antimutagenic activities of isofraxinellone against furylfuramide and Trp-P-l were tested by an Ames test using Salmonella typhimurium TA100, which indicated that isofraxinellone showed antimutagenic activity.