An Azasterol that Inhibits Cholesterol Synthesis in vitro.

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Abstract
A series of azasterols structurally related to cholesterol has been synthesized to test the hypothesis that they might mimic the action of cholesterol in regulating endogenous sterol synthesis as proposed in the negative feedback hypothesis of Siperstein and Guest (J. Clin. Invest. 38: 1043, 1959). An in vitro screening test revealed several active compounds. From this series SC-11952, or 22,25-diazacholestanol dihydrochloride, was selected for more extensive characterization. In rat liver homogenate SC-11952 inhibited acetate- 1-C incorporation into cholesterol to a much greater extent than when mevalonate-2-C14 was used as the substrate. The compound did not affect the Q02 nor the conversion of acetate-1-C14 to Cl4o2; but, concomitant with the reduction of sterol synthesis, there were increased amounts of fatty acid and of keto acid C14 detected. The data are interpreted as evidence that the primary action of SC-11952 may be to inhibit hydroxy-methyl-glutaryl-CoA reductase.