Mevalonic acid analogs as inhibitors of cholesterol biosynthesis

C. Rowan DeBold,

C. Rowan DeBold

Department of Biochemistry, State University of New York, Upstate Medical Center, Syracuse, NY 13210

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J. C. Elwood,

Corresponding Author

J. C. Elwood

Department of Biochemistry, State University of New York, Upstate Medical Center, Syracuse, NY 13210

Department of Biochemistry, State University of New York, Upstate Medical Center, Syracuse, NY 13210Search for more papers by this author

C. Rowan DeBold,

C. Rowan DeBold

Department of Biochemistry, State University of New York, Upstate Medical Center, Syracuse, NY 13210

Search for more papers by this author

J. C. Elwood,

Corresponding Author

J. C. Elwood

Department of Biochemistry, State University of New York, Upstate Medical Center, Syracuse, NY 13210

Department of Biochemistry, State University of New York, Upstate Medical Center, Syracuse, NY 13210Search for more papers by this author

First published: September 1981

https://doi.org/10.1002/jps.2600700910

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Abstract

A series of 20 mevalonic acid analogs was synthesized and tested for their ability to inhibit cholesterol biosynthesis from [2-¹⁴C]-mevalonate in rat liver homogenates. Removal of the 5-hydroxyl group from mevalonic acid produced an active inhibitor, 3-hydroxy-3-methylpentanoic acid. Removal of the 3-hydroxyl group, addition of an aromatic group in the 3-position, or insertion of a double bond reduced inhibitory activity. Compounds with an aromatic group or halide on the 5-position were active inhibitors. The most active inhibitor was 5-phenylpentanoic acid, with 50% inhibition at 0.064 mM.

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Volume70, Issue9

September 1981

Pages 1007-1010

Mevalonic acid analogs as inhibitors of cholesterol biosynthesis

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Mevalonic acid analogs as inhibitors of cholesterol biosynthesis

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