Galbanic Acid, a Cytotoxic Sesquiterpene from the Gum Resin of Ferula asafoetida, Blocks Protein Farnesyltransferase

Abstract

Farnesylation of the activated ras oncogene product by protein farnesyltransferase (FTase) is a critical step for its oncogenic function. Bioassay-guided purification of Ferula asafoetida (Umbelliferae) extract led to the isolation of the coumarin-derived sesquiterpene galbanic acid (1) as an active principal for FTase inhibitory activity, together with the four structurally related sesquiterpenes karatavicinol (2), umbelliprenin (3), farnesiferol B (4), and farnesiferol C (5). The 50 % inhibitory concentration (IC₅₀) of 1 against FTase in an enzyme-based assay was calculated as 2.5 µM. Compound 1 also demonstrated potent inhibition of the proliferation of oncogenic ras-transformed NIH3T3/Hras-F in a dose-dependent manner. The IC₅₀ value of 1 on the proliferation of oncogenic ras-transformed NIH3T3/Hras-F cells was calculated as 16.2 µM, whereas its IC₅₀ value on control vector-transfected normal ras-containing NIH3T3/ZIPneo cells was 58.5 µM.

Ferula asafoetida - Umbelliferae - farnesyltransferase inhibition - FTase - galbanic acid

References

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