Prenylated Bibenzyls from the Chinese Liverwort Radula constricta and Their Mitochondria-Derived Paraptotic Cytotoxic Activities

Nine new prenylated bibenzyls, radstrictins A–I (1–9), and 11 known congeners were obtained from the Chinese liverwort Radula constricta. Their structures were identified by analysis of HRMS, NMR, and electronic circular dichroism data. Radstrictins A–F (1–6) were isolated as a racemate or scalemic mixtures. All the isolated compounds were subjected to cytotoxicity assessment. Methyl 2,4-dihydroxy-3-(3-methyl-2-butenyl)-6-phenethylbenzoate (10) exhibited significant activity against human lung cancer cell lines A549 and NCI-H1299 with IC₅₀ values of 6.0 and 5.1 μM, respectively. Further research revealed that cell death triggered by 10 occurred via mitochondria-derived paraptosis.