Abstract: Anticancer compounds based on previously known irreversible and reversible inhibitors of farnesyltransferase were designed and synthesized. These contained alpha-dicarbonyl or boronic acid moieties previously shown to irreversibly bind farnesyltransferase. Three classes of compounds were developed to probe the use of these moieties in the farnesyltransferase active site: terphenyldiglyoxals, biphenylglyoxals, and phenylboronic acids. Each of these classes inhibited farnesyltransferase to varying degrees, and structure-activity relationships were established for their efficacy. Moreover, selected compounds from each group inhibited cancer cell growth in vitro. Generally, their cell growth inhibition was greater than would be predicted based upon the farnesyltransferase inhibition data. The phenylboronic acids were micromolar inhibitors of cancer cell line growth despite being slightly insoluble in the incubation mixture. Also, a new class of potent anticancer compounds, chalcone epoxides, was invented as potential tubulin inhibitors. One compound was analyzed by use of x-ray crystallography. A structure-activity relationship analysis of the class was attempted but fell short due to synthesis and purification problems. One compounds of this type, however, was shown not to be a farnesyltransferase inhibitor, although it inhibited cancer cell growth. Finally, a very potent polymethoxylated benzil based on a previously discovered beta tubulin polymerization inhibitor displayed impressive IC50 values ranging from 110–2000 nM against cancer cell lines in vitro. The synthesis of this compound had a low yield despite varied approaches. Solutions to this problem are postulated.