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

Abstract

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 IC50 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.