Novel cytotoxic labdane diterpenes from Marrubium cylleneum

In continuation of our phytochemical investigations into Marrubium species of the Greek flora [1], we report on the isolation and identification of further novel secondary metabolites from the dichloromethane extract from the aerial parts of Marrubium cylleneum Boiss. & Heldr.. One labdane diterpene (1) and one labdane nor-diterpene (2) have been isolated along with β-sitosterol and palmitic acid. The structures of the isolated compounds were established by means of 1D & 2D NMR and MS spectral analyses. Both new and previously isolated diterpenes were tested for their immunomodulating potential in standard in vitro cytotoxicity assays [2]. Peripheral blood mononuclear cells (PBMC) from normal donors and cancer patients were isolated and subsequently incubated with low concentrations of each compound for 1–3 days. Effectors PBMC were further assayed for enhancement of their lytic ability against ⁵¹Cr-labeled target cells (K562, Daudi and Jurkat) at effect or to target ratios varying between 10–80:1. Some of these compounds could be potentially used to enhance PBMC anticancer activity, as they enhance immune responses of human lymphocytes, inducing cell proliferation and augmenting their cytotoxicity against tumor targets, whereas at the same time they present significant antitumor activity, efficiently lysing leukemic cells.

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References: 1. Karioti, A. et al. (2005), Phytochemistry 66: 1060–1066. 2. Tsavaris, N.B. et al. (2004), Oncology 67: 403–410.