Unprecedented nor-seco -polycyclic polyprenylated acylphloroglucinols counteract myocardial cell injury via activation of the Akt/mTOR signaling pathway

Hypermonols A–E (1–5), which are highly modified nor-seco -polycyclic polyprenylated acylphloroglucinols with an unprecedentedly linear 5-5/6/5 tetracyclic skeleton, were isolated from Hypericum monogynum . Their structures including absolute configurations were elucidated via spectroscopic analyses, comparison of electronic circular dichroism data, quantum chemical calculations, and single-crystal X-ray diffraction analyses. In addition, we have firstly confirmed and distinguished that the 24 R and 24 S configuration exist in sec -Bu-containing PPAPs via R 2 values, MAE ΔΔ δ analysis, and CP3 calculations based on the experimental and calculated NMR data of 3 and 4, a pair of 24-epimers, which might provide an insight into the configurational determination of sec -Bu-containing PPAPs. Structure-pharmacophore-based virtual screening in ePharmaLib, as well as molecular docking and western blot analysis, imply that 1 may elicit its protective effect against H 2 O 2 -induced myocardial cell injury via activation of the Akt/mTOR signaling pathway.