Bioactivity-Guided Isolation of Totarane-Derived Diterpenes from Podocarpus neriifolius and Structure Revision of 3-Deoxy-2α-hydroxynagilactone E.

Bioactivity-guided phytochemical investigation of Podocarpus neriifolius D. Don. (Podocarpaceae) has led to the isolation of one new (2) and three known (1, 3, and 4) B-type podolactones, along with three totarane-type diterpenes (5-7). Their structures were determined by interpretation of High Resolution ElectroSpray Ionization Mass Spectrometry (HRESIMS) and 1D and 2D NMR data, and comparison with the values reported in the literature. The structure of compound 1, previously identified as 3-deoxy-2α-hydroxynagilactone E (8), was revised as its 2β-epimer, which has been reported recently as a new compound. All of the isolates were evaluated for their antiproliferative activity against a panel of four human cancer cell lines, namely, ovarian (OVCAR3), breast (MDA-MB-231), colon (HT-29), and melanoma (MDA-MB-435), and compounds 1 and 3 were found to be cytotoxic with IC values in the low micromolar range for most of the cell lines used. The major compound, inumakilactone A (3), was further tested in vivo using the HT-29, MDA-MB-435, and OVCAR3 cells in a murine hollow fiber model, for the first time.