CP-225, 917 and CP-263, 114, Novel Ras Farnesylation Inhibitors from an Unidentified Fungus

I. Taxonomy, Fermentation, Isolation, and Biochemical Properties

抄録

During the course of our screening for squalene synthase inhibitors and Ras farnesylation inhibitors, a novel fungal culture was discovered to produce two structurally unique compounds, CP-225, 917 and CP-263, 114, as well as zaragozic acid A (squalestatin I). The two compounds are characterized by a bicyclo[4.3.1]dec-1, 6-diene core plus two extended alkyl chains. CP-225, 917 and CP-263, 114 inhibit Ras farnesyl transferase from rat brain with IC₅₀ values of 6μM and 20 μM, respectively. CP-225, 917 inhibits squalene synthase with an IC₅₀ value of 43 μM and CP-263, 114 with an IC₅₀ of 160μM. The producing organism, though not fully classified, exhibits the characteristics of a sterile Phoma species.