Phenol derived CVFM analogs inhibitors of ras farnesyl transferase possessing cellular in vitro activity.

A study was performed on structure-activity relationships of a series of phenol-derived CVFM analogs as inhibitors of ras Farnesyltransferase (FTase). The effect of various substituents on the phenol ring was examd., while the VFM moiety of the potent inhibitor CVFM was kept const. The FTase inhibitory activity, reported as IC50, was influenced by both the chem. properties and the relative position of the substituents on the phenolic ring. The most active compds. in this series contained a chloro or bromine substituent on the phenolic ring. Subsequently the authors have tested the effects of these FTase inhibitors on the anchorage-dependent growth of two rat epithelial cell lines, FRTL-5 and the same line v-Ha-ras transformed. While most of the compds. were inactive, two showed a growth inhibitory effect: I was active against normal as well against transformed cells while II was active only against transformed cells.