CYLINDROL-A - A NOVEL INHIBITOR OF RAS FARNESYL-PROTEIN TRANSFERASE FROM CYLINDROCARPON LUCIDUM

Farnesylation of Ras (p21) protein by farnesyl-protein transferase (FP Tase) is essential for cell-transforming activity in several tumor-typ es. Inhibition of FPTase activity has been shown to inhibit ras- depen dent cell transformation and tumor size in nude mice thereby validatin g FPTase as a potential target for anticancer drugs. Our continued sea rch for such inhibitors led to the isolation of cylindrol A, a bicycli c resorcinaldehyde cyclohexanone propionate derivative, from Cylidroca rpon lucidum. The isolation, structure elucidation by NMR and X-ray cr ystallographic methods, stereochemistry and FPTase activity of cylindr ol A are described.