Thirteen coumarins (1–13), including five new compounds (1–5), were isolated from the folk medicinal plant Poncirus trifoliata. Combined spectroscopic analyses revealed
that coumarins 1–4 are bis-isoprenylated
coumarins with diverse oxidation patterns, while 5 is
an enantiomeric di-isoprenylated coumarin. The absolute configurations
of the stereogenic centers in the isoprenyl chains were assigned through
MTPA and MPA methods, and those of the known compounds triphasiol
(6) and ponciol (7) were also assigned using
similar methods. These coumarins inhibited significantly Staphylococcus
aureus-derived sortase A (SrtA), a transpeptidase responsible
for anchoring surface proteins to the peptidoglycan cell wall in Gram-positive
bacteria. The present results obtained indicated that the bioactivity
and underlying mechanism of action of these coumarins are associated
with the inhibition of SrtA-mediated S. aureus adhesion
to eukaryotic cell matrix proteins including fibrinogen and fibronectin,
thus potentially serving as SrtA inhibitors.