Oreganic acid: a potent novel inhibitor of ras farnesyl-protein transferase from an endophytic fungus

Inhibitors of farnesyl-protein transferase (FPTase) have the potential of being anticancer agents for tumors in which ras is found mutated and contributes to cell transformation. From the screening of the extracts of an endophytic fungus isolated from living leaves of Berberis oregana, we have discovered the tricarboxylated alkylsulfate, oreganic acid (1), as a potent (IC50 = 14 nM) and specific inhibitor of FPTase. Its desulfated analog (4) was less active (IC50 = 3.3μM). The trimethylester (2) and its desulfated analog (3) were inactive.