Dimethylated acylphloroglucinol meroterpenoids with anti-oral-bacterial and anti-inflammatory activities from Hypericum elodeoides

Abstract

Acylphloroglucinol meroterpenoids are adducts of the acylphloroglucinol unit and polyprenylated fragments (terpenoids) with attractive structures and bioactivities. During study of the medicinal molecules of the genus Hypericum, the first example of dimethylated acylphloroglucinol meroterpenoids with pyran-fused 6/6/6 tricyclic skeletons ((+)/(−)-elodeoidols A-F (1–6)), along with three biogenetical homologues (7–9) were isolated from the herbaceous plant of Hypericum elodeoides. Their structures including absolute configurations were then identified by nuclear magnetic resonance (NMR), high resolution electrospray ionization mass spectroscopy (HRESIMS), electronic circular dichroism (ECD) analysis and calculations. The monoterpene moiety of 1–6 were cyclized as two cyclohexanes and fused with a dimethylated acylphloroglucinol unit through an additional ether linkage, which led to an interesting pyran-fused linear or angle type 6/6/6 tricyclic skeleton. Compounds 5, 8 and 9 showed preferable antibacterial activities against three oral bacteria, among the MIC value of (+)-5 was 6.25 μg/ml; Compounds 3, 7 and 8 exhibited significant NO inhibitory activity against LPS induced RAW264.7 cells (IC50: 10.39 ± 0.49 ~ 34.25 ± 2.32 μM).