Triterpene and diterpene inhibitors of pyruvate dehydrogenase kinase (PDK)

• Published in: Bioorganic & medicinal chemistry letters Vol. 9; no. 15; pp. 2223 - 2228
• Main Authors: Aicher, Thomas D., Damon, Robert E., Koletar, Judit, Vinluan, Christine C., Brand, Leonard J., Gao, Jiaping, Shetty, Suraj S., Kaplan, Emma L., Mann, William R.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 02.08.1999; Elsevier
• Subjects: Administration, Oral; Animals; Biological and medical sciences; Blood Glucose - drug effects; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - metabolism; Disease Models, Animal; Diterpenes - chemical synthesis; Diterpenes - pharmacology; Diterpenes - therapeutic use; General and cellular metabolism. Vitamins; Medical sciences; Mice; Pharmacology. Drug treatments; Protein Kinase Inhibitors; Protein Kinases; Protein-Serine-Threonine Kinases; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship; Triterpenes - chemical synthesis; Triterpenes - pharmacology; Triterpenes - therapeutic use; Endocrinopathy; Steroid; Enzyme; Transferases; Diabetes mellitus; Rodentia; Oral administration; Enzyme inhibitor; Cetoxime; [Pyruvate dehydrogenase (lipoamide)] kinase; Vertebrata; Hypoglycemic agent; Terpene; Mammalia; Structure activity relation; Mouse; Animal; Triterpene; Diterpene; Aromatic compound; Chemical synthesis; Allenic compound
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(99)00380-7

Several oximes of triterpenes with a 17-β hydroxyl and abietane derivatives are inhibitors of pyruvate dehydrogenase kinase (PDK) activity. The oxime 12 and dehydroabietyl amine 2 exhibit a blood glucose lowering effect in the diabetic ob/ob mouse after a single oral dose of 100 μmol/kg. However, the mechanism of the blood glucose lowering effect is likely unrelated to PDK inhibition. Several oximes of triterpenes with a 17-β hydroxyl and abietanes are inhibitors of pyruvate dehydrogenase kinase (PDK) activity. The oxime 12 and dehydroabietyl amine 2 exhibit a blood glucose lowering effect in the diabetic ob/ob mouse after a single oral dose of 100 μmol/kg. However, the mechanism of the blood glucose lowering effect is likely unrelated to PDK inhibition.