Unprecedented Monoterpenoid Polyprenylated Acylphloroglucinols with a Rare 6/6/5/4 Tetracyclic Core, Enhanced MCF-7 Cells' Sensitivity to Camptothecin by Inhibiting the DNA Damage Response

(+/-)-Hypersines A-C (1-3), the three pairs of enantiomerically pure monoterpenoid polyprenylated acylphloroglucinols with an unprecedented 6/6/5/4 fused ring system, were isolated from Hypericum elodeoides. Their structures, including absolute configurations, were elucidated by comprehensive spectroscopic data, single-crystal X-ray diffraction, and quantum chemical calculations. The plausible, biosynthetic pathway of 1-3 was proposed. Moreover, the bioactivity evaluation indicated that 1a might be a novel DNA damage response inhibitor, and could enhance MCF-7 cell sensitivity to the anticancer agent, camptothecin.