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Several 15-oxygenated sterols were examined as to their inhibitory activity toward cholesterol synthesis from [24,25-3H]-24,25-dihydrolanosterol in the 10,000 X g supernatant fraction of a rat liver homogenate. At 40 microM, three 15 alpha-hydroxylated compounds, 14 alpha-ethylcholest-7-ene-3 beta,15 alpha-diol, 14 alpha-methylcholest-7-ene-3 beta,15 alpha-diol, and lanost-7-ene-3 beta,15 alpha-diol, were found to be extremely potent inhibitors (more than 90% inhibition) of dihydrolanosterol metabolism. The inhibitory effect of the C-15 substituents appeared to be in the order of: 15 alpha-hydroxyl greater than 15-ketone greater than 15 beta-hydroxyl.
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