Cyclopentabenzofuran Lignan Protein Synthesis Inhibitors from Aglaia odorata

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Abstract
In the course of screening for Ras function inhibitors, rocaglaol (1) and the related compounds, the known pyrimidinone (2) and the novel aglaiastatin (3), were isolated from a CHCl3 extract of the leaves of Aglaia odorata. The structure of 3 was elucidated as a novel cyclopentabenzofuran on the basis of its NMR spectroscopic data and by X-ray crystallographic 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 induced normal morphology in K-ras-NRK cells at 10−30 ng/mL. They also specifically 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 synthesis.