title: Cyclopentabenzofuran lignan protein synthesis inhibitors from Aglaia odorata.
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 CHCI3 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.
authors: Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.
authors: T
authors: T
authors: Ohse
authors: S
authors: S
authors: Ohba
authors: T
authors: T
authors: Yamamoto
authors: T
authors: T
authors: Koyano
authors: K
authors: K
authors: Umezawa
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000302:isolation & purification* / Q000494:pharmacology; D002460:Cell Line; D018360:Crystallography, X-Ray; D004247:DNA / Q000096:biosynthesis; D015151:Immunoblotting; D009682:Magnetic Resonance Spectroscopy; D018515:Plant Leaves / Q000737:chemistry*; D010946:Plants, Medicinal / Q000737:chemistry*; D011500:Protein Synthesis Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D013056:Spectrophotometry, Ultraviolet; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000096:biosynthesis
chemical_list: D001572:Benzofurans; D011500:Protein Synthesis Inhibitors; D012313:RNA; D004247:DNA; D018631:ras Proteins