Pentacyclic triterpene acids, rotungenic acid and barbinervic acid, from fresh leaves of Diospyros kaki Thunberg and their glutaminase inhibitory activities.

Glutaminase is an important target that is often over-expressed in neurodegenerative and lifestyle-related diseases but few effective inhibitors of this enzyme have yet reached clinical trials. Three compounds isolated from fresh leaves of Diospyros kaki Thunberg, ursolic acid ( 1 ), rotungenic acid ( 2 ) and barbinervic acid ( 3 ), were identified by analyzing their NMR and MS spectral data and comparison of these with reported data. The IC 50 values of 1 - 3 and 6-diazo-5-oxo-L-norleucine (DON) as control were 775, 13, 14, and 434 μM, respectively. Compounds 2 and 3 showed higher glutaminase inhibitory activities than DON. Compounds 2 and 3 may serve as potential lead compounds for the prevention and treatment of neurodegenerative and lifestyle-related diseases by targeting glutaminase. This is the first report on glutaminase inhibitory activities of 2 and 3 .