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

Abstract

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 IC50 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.Graphical Abstract Electronic supplementary materialThe online version of this article (10.1007/s13659-019-0198-x) contains supplementary material, which is available to authorized users.

Anticancer Activities and Mechanism of Action of Nagilactones, a Group of Terpenoid Lactones Isolated from Podocarpus Species

“…Structure-anticancer activity relationships in the Nag-E series. The indicated IC 50 values (mM) correspond to the compound concentrations required to reduce proliferation of human epithelial carcinoma A431 cells by 50%, as described by Zheng et al [15] quantity of 3-deoxy-2β-hydroxy-nagilactone E was not sufficient for in vivo testing [32]. Proofs of anticancer activities of nagilactones in vivo are limited.…”

“…The related compound inumakilactone A, which is less active than deoxy-2β-hydroxy-nagilactone E in vitro, was found to be inactive in an in vivo hollow fiber assay using the same cell lines. Unfortunately, the available quantity of 3-deoxy-2β-hydroxy-nagilactone E was not sufficient for in vivo testing [ 32 ].

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