Staphylococcus aureus relies on quorum sensing to exert virulence to establish and maintain infection. Prior research demonstrated the potent quorum sensing inhibition effects of “430D-F5”, a refined extract derived from the fruits of Schinus terebinthifolia, a medicinal plant used for the traditional treatment of skin and soft tissue infections. We report the isolation and identification of three compounds from 430D-F5 that reduce virulence and abate dermonecrosis: 3-oxo-olean-12-en-28-oic acid (1), 3-oxotirucalla-7,24Z-dien-26-oic acid (2) and 3α-hydroxytirucalla-7,24 Z-dien-27-oic acid (3). Each compound inhibits all S. aureus accessory gene regulator (agr) alleles (IC₅₀ 2–70 μM). Dose-dependent responses were also observed in agr-regulated reporters for leucocidin A (lukA, IC₅₀ 0.4-25 μM) and glycerol ester hydrolase or lipase (gehB, IC₅₀ 1.5–25 μM). Surprisingly, dose-dependent activity against the nuclease reporter (nuc), which is under the control of the sae two-component system, was also observed (IC₅₀ 0.4–12.5 μM). Compounds 1-3 exhibited little to no effect on the agr-independent mgrA P2 reporter (a constitutive promoter from the mgrA two-component system) and the esxA reporter (under control of mgrA). Compounds 1-3 inhibited δ-toxin production in vitro and reduced dermonecrosis in a murine in vivo model. This is the first report of triterpenoid acids with potent anti-virulence effects against S. aureus.

The natural compound Genkwanin (systematic name: 5-hydroxy-2-(4-hydroxyphenyl)-7-methoxychromen-4-one) C₁₆H₁₂O₅ (1) is a non-glycosylated flavonoid isolated from Callicarpa americana. Microcrystals of Genkwanin were prepared by slow evaporation of a methanol solution under low temperature conditions. The structure of 1 was determined based on spectroscopic analyses, one-dimensional NMR, HRESIMS and was confirmed by single-crystal X-ray diffraction. The crystals grow as very thin needles with an extremely high aspect ratio and with the long axis (along the y-axis) corresponding to the very short unit cell b-axis. There are two independent molecules in the asymmetric unit with two different conformations and modes of packing in the crystal. One molecule has a higher degree on non-planarity than the other. The short stacking distance and separation between the molecules implies a high degree of co-planarity consistent with a conjugated system. The crystal structure is non-centrosymmetric but achiral.