CYCLOPENTABENZOFURAN LIGNAN PROTEIN-SYNTHESIS INHIBITORS FROM AGLAIA-DORATA

In the course of screening for Ras function inhibitors, rocaglaol (1) and the related compounds, the known pyrimidinone (2) and the novel ag laiastatin (3), were isolated from a CHCl3 extract of the leaves of Ag laia odorata. The structure of 3 was elucidated as a novel cyclopentab enzofuran on the basis of its NMR spectroscopic data and by X-ray crys tallographic analysis. These compounds (1-3) were potent inhibitors of the growth of K-ras-NRK cells, with IC50 values of 1-10 ng/mL, and in duced normal morphology in K-ras-NRK cells at 10-30 ng/mL. They also s pecifically inhibited protein synthesis. Aglaiastatin (3) was slightly more potent than 1 and 2 in inhibiting cell growth. Aglaiastatin (3) reduced the amount of Ras, possibly by inhibiting its de novo synthesi s.