Siegesoxylipin A‒J, previously undescribed phyto-oxylipins inhibition of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci from Sigesbeckia orientalis

Abstract

Ten previously undescribed phyto-oxylipins siegesoxylipin A‒J (1–10), along with four known analogs (11–14), were isolated from the aerial parts of Sigesbeckia orientalis. The elucidation of their structures was accomplished through spectroscopic analyses, base-catalyzed hydrolysis and X-ray diffraction. Moreover, unmethylesterified 4-methylpentanoic acid siegesoxylipins 1, 2, and 4–7 exhibited potent inhibitory bioactivity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) strains with MIC values of 8 μg/mL, in which siegesoxylipin A (1) inhibited bacteria by inducing membrane damage. Siegesoxylipins represent an original class of anti-MRSA and anti-VRE agents with 4-methylpentanoates incorporating fatty acid moieties. This discovery holds promise for the development of new therapeutic strategies to combat antibiotic-resistant infections.