New antiproliferative trihydroxyalkylcyclohexenones from Pleiogynium timoriense

The former Merck collection of natural product extracts is now managed by the Natural Products Discovery Institute, and the authors have initiated a collaborative investigation of this collection as a potential source of new drug leads. In our initial investigation, a dichloromethane partition of the ethanol extract of the bark of Pleiogynium timoriense was selected for investigation because of its strong antiproliferative activity against the A2780 human ovarian cancer cell line (IC₅₀ 1.3µg/mL). The three new bioactive trihydroxyalkylcyclohexenones 1–3 have been isolated by bioassay-directed fractionation using solid phase extraction and HPLC methods. The structures were determined using spectroscopic and chemical methods. All three compounds exhibited antiproliferative activity against the A2780 human ovarian cancer cell line with IC₅₀ values of 0.2, 1.9 and 0.5µg/mL, respectively. The absolute configurations of the isolated compounds were determined using spectroscopic evidence and chemical modification.