Antiproliferative diterpenoids from the roots of Podocarpus neriifolius

Plant samples collected in the Southeast Asian rainforests were subjected to initial screening against the HT-29 human colon cancer cell line, and Podocarpus neriifolius D. Don (Podocarpaceae), obtained from Vietnam, with an IC50 value of 8.2 µg/mL, was selected for further investigation aiming for the discovery of potential anticancer lead agents. Bioactivity-guided purification of the active ethyl acetate fraction (IC50= 4.3 µg/mL) from the dried root sample of P. neriifolius has so far afforded three type-B podolactones, namely, makilactones E (1) and G (2) and inumakilactone A (3), all characterized by the presence of a 7α,8α-epoxy-9(11)-enolide functionality [1 – 3]. Their structures were determined by interpretation of spectroscopic data and comparison with the existing literature [1,2]. In addition, the X-ray crystallography data of 1 was obtained to confirm its absolute configuration. While 3 has shown termiticidal and cytotoxic activity against murine leukemia cells P388 in vitro [1,2], in this study, it exhibited potent activity against HT-29 with an IC50 value of 1.1µM. On the other hand, compounds 1 and 2 were non-cytotoxic in this assay. In this presentation, the isolation and structure determination of these compounds are described as well as the dereplication of additional active sub-fractions, which suggests the presence of different active podolactones and totarane-type diterpenes.