Gonystylones A-E, Antiproliferative 5,6-Dihydro-α-pyrones from the Plant Gonystylus borneensis

A high-throughput screening campaign designed to discover natural product inhibitors of rhabdomyosarcoma oncogene PAX3-FOXO1 gene expression identified partially purified fractions from an organic extract of the plant Gonystylus borneensis to have potent activity in the assay. Bioassay-guided isolation yielded five new 5,6-dihydro-α-pyrone natural products, namely, gonystylones A-E (1-5). Their structures were elucidated using 1D and 2D NMR experiments and their absolute configurations determined using semisynthetic and electronic circular dichroism methods. The gonystylones were found to be cytotoxic to rhabdomyosarcoma cells at low micromolar concentrations (3-19 μM).