Hyperattenins A–I, bioactive polyprenylated acylphloroglucinols from Hypericum attenuatum Choisy

Abstract

Nine new polyprenylated acylphloroglucinols (PPAPs), hyperattenins A–I (1–9), together with thirteen known analogues (10–22), were isolated from the aerial parts of Hypericum attenuatum Choisy. The structures of 1–9 were elucidated by extensive spectroscopic analysis. The absolute configuration of 1 was determined by a single X-ray crystallographic analysis, and the absolute configurations of 2–9 were determined by comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Compound 1 was characterised as a bicyclo[3.3.1]nonane derivative containing an unusual hemiacetal functionality formed by a series of redox reactions on its side chains, which occurs rarely in nature. All new isolates were evaluated for cytotoxic activities against several human cancer cell lines. Compound 9 exhibited significant inhibitory activity against the HL-60 and A-549 cell lines, with IC₅₀ values of 2.04 and 3.26 μM, respectively. Compound 9 also showed low toxicity to Beas-2B cells (IC₅₀ = 14.36 μM), suggesting that it could be a selective anti-tumour agent for leukaemia and lung cancer. Compounds 2–8 were also screened for their anti-HIV-1 activities.