The squalestatins: potent inhibitors of squalene synthase. The role of the tricarboxylic acid moiety

In squalestatins possessing at C6 either a 4,6-dimethyloctenoate ester or a hydroxyl group, the 5-carboxylic acid is crucial for squalene synthase inhibitory activity. In the former seires, free carboxylic acids are not required at C3 or C4 for potent enzyme inhibitory activity whereas in the latter series esterification of the carboxylic acids at C3 or C4 results in a significant reduction in enzyme inhibitory activity.