posted on 2023-11-28, 07:14authored byYong Zhao, Tuo Li, Louise Kjaerulff, Henrietta Venter, Sonia Coriani, Birger Lindberg Møller, Susan Semple, Dan Staerk
Serrulatanes
constitute a class of unique diterpenoids derived
from all-Z nerylneryl diphosphate rather than the
conventional all-E diterpenoid precursor geranylgeranyl
diphosphate and thus provide an intriguing expansion of the chemical
space of plant specialized metabolites. Plants of the Australian Eremophila genus are rich sources of structurally diverse
serrulatanes. Here, we report the identification of 15 hitherto undescribed
serrulatanes (eremoculatanes A–N), together with 16 previously
reported compounds, from the EtOAc extract of Eremophila denticulata leaves. Isolation was performed by a combined use of systematic
HPLC-PDA-HRMS-based phytochemical profiling and orthogonal reversed-phase
C18 and pentafluorophenyl separations. Among the new compounds
isolated, eremoculatane A contains a C12 backbone, for
which the configuration was established by comparison of experimentally
measured and theoretically calculated ECD spectra. The antihyperglycemic
and antibacterial activities of the E. denticulata extract were investigated by high-resolution inhibition profiling,
and they indicated that major constituents, mainly serrulatanes and
flavonoids, contributed to the observed activity of the extract. One
flavonoid, eupafolin (4), displayed moderate α-glucosidase
inhibitory activity with an IC50 value of 41.3 μM,
and four serrulatanes (8, 9, 19g, and 19j) showed more than 50% PTP1B inhibition at
200 μM.