well as among structurally similar compounds such as citreohybridones, suggested that the inhibitory activity is greater when a methoxy or acetoxy residue is attached to the C-15 position rather than to the C-17 position ofmeroterpenoid ring. In addition, the FTase inhibition by andrastins appears to be reversible. Thus, this family of meroterpenoids provides a group of compounds useful for further probing the active site of FTase. Kurasoins A and B were found from the culture broth of Paecilomyces sp. FO-3684

(68). This fungus was isolated from a soil sample collected at Kurashiki City, Japan. Both compounds are acyloin compounds and have a 3-hydroxy-1-phenyl-2-butanone moiety in common. The IC50 values of kurasoins A and B against FTase were 59 and 58.7 ^M, respectively. These values are rather high and suggest that they may not be good FTase inhibitors. However, total synthesis ofthese compounds has recently been accomplished

(69) and derivatives with higher potency may be obtained in the future. Saquayamycin E and F were isolated from the Actinomycetes strain MK290-AF1 (70).

They belong to a family of compounds called saquayamycins, which include saquayamycin A,B, C, and D. These compounds as well as the related compound aquayamycin all exhibit the ability to inhibit FTase (70), and their IC50 values are between 1 and 2 ^M. Kinetic analysis with Lineweaver-Burk plotting suggested that the Saquayamycins non-competitively inhibit the enzyme with respect to the Ras protein substrate.

In conclusion, a large number of natural products have been identified that exhibit FTase inhibitory activity. However, the potency is generally low with the IC50 value in the ^M range. Although these natural compounds are useful as lead compounds, extensive study to identify derivatives is necessary to obtain compounds with increased potency. Another caution concerning natural products is their possible toxicity towards mammalian cells. This is particularly true for antibiotics that have been shown to exhibit antibacterial or anti-fungal activities. Any toxicity associated with the compound needs to be critically evaluated to see whether the inhibitory activity against FTase is separated from the toxic activity before further tests can be conducted.

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