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

Abstract

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 24R and 24S configuration exist in sec-Bu-containing PPAPs via R² values, MAE_ΔΔδ 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 H₂O₂-induced myocardial cell injury via activation of the Akt/mTOR signaling pathway.