Anti-invasive and cytotoxic evaluation of a (+)-pinoresinol-based semisynthetic library against glioblastoma

The Australian endemic plant genus Eremophila has long been recognized for its unique chemical diversity, with numerous novel and bioactive compounds reported. In this study, we chemically investigated the seeds of Eremophila maculata for the first time, which led to the isolation and characterization of two known plant metabolites, (+)-salicifoliol and (+)-pinoresinol. Due to the reported biological properties of the lignan natural product (+)-pinoresinol and its high abundance from the seeds of E. maculata , we synthesized five analogues for biological evaluations. Preliminary cytotoxicity evaluations of the semisynthetic pinoresinol-based library against two human glioblastoma cell lines, U251MG and KNS42, showed (+)-4,4'-di(3,3-dimethylbutanoyl)pinoresinol had slight cytotoxicity at 10 µM. A transwell anti-invasive assay on the same compound showed a reduction in the invasion of adult U251MG cells by 50% and pediatric KNS42 cells by 30%, with IC 50 values of 0.26 and 0.40 µM, respectively.