np7b01082_si_001.pdf (8.43 MB)
Isolation, Characterization, and Structure–Activity Relationship Analysis of Abietane Diterpenoids from Callicarpa bodinieri as Spleen Tyrosine Kinase Inhibitors
journal contribution
posted on 2018-03-23, 22:04 authored by Jun-Bo Gao, Shuang-Jing Yang, Zi-Ru Yan, Xing-Jie Zhang, De-Bing Pu, Li-Xia Wang, Xiao-Li Li, Rui-Han Zhang, Wei-Lie XiaoSpecies belonging to the genus Callicarpa are used traditionally in Chinese medicine for
the treatment of inflammation, rheumatism, and pain. Investigation
of the leaves and twigs of Callicarpa bodinieri resulted
in the isolation of nine new abietane diterpenoids, bodinieric acids
A–I (1–9), along with six
known compounds (10–15). The structures
of 1–9 were elucidated on the basis
of the interpretation of their HRESIMS and NMR data and by ECD calculations.
To explore the potential therapeutic target of this plant for immune-mediated
disease, the inhibitory activities of the isolates obtained were determined
against 13 kinase enzymes. Eight compounds exhibited moderate inhibitory
effects on spleen tyrosine kinase (SYK), and the IC50 values
of compounds 2 and 6 were 7.2 and 10.7 μM,
respectively. In addition, a preliminary structure–activity
relationship of this scaffold was analyzed with both molecular docking
and a 3D-QSAR pharmacophore model.