Antitumorigenic agent

The chaetomellic acids A and B (43 and 44), isolated from Chaetomella acutiseta found in seeds of peas, are potent and highly specific famesyl-mimic inhibitors of ras farnesyl-protein transferase. Farnesylation by this enzyme is the first and obligatory step for the post-translational modification of ras. The modified ras protein appears to be involved in tumorigenesis (approximately 25% of tumours) and there is evidence that inhibitors of the transferase have the potential to be antitumorigenic agents. These metabolites can be considered to be assembled by condensation of a palmitoyl and oleic acid chain C2 with pyruvate or oxaloacetate (Scheme 2) [38, 39]. Two syntheses have been reported for chaetomallic acid A [39, 40], one of which is patterned on the probable biogenesis [39]. 

Like many other antioxidants, rosemary and its polyphenols possess not only antioxidative activities, but also antitumorigenic activities. Huang et al. (5) investigated the inhibitory effects of rosemary extract, carnosol and ursolic acid on tumor formation in mouse skin. They found that topical application of rosemary inhibits B(a)P- and DMBA-induced initiation of tumor and TPA-induced tumor promotion in DMBA-initiated mice. Carnosol and ursolic acid were found to be strong inhibitors of TPA-induced inflammation, ornithine decarboxylase activity and tumor promotion in mouse skin (5). It was suggested that carnosol acted like other nonsteroidal phenolic anti-inflammatory agents, such as curcumin, which inhibited the metabolism of arachidonic acid. 

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