Cytotoxic compounds from the leaves and stems of the endemic Thai plant Mitrephora sirikitiae

CONTEXT: Mitrephora sirikitiae Weeras., Chalermglin & R.M.K. Saunders (Annonaceae) is a plant endemic to Thailand. Its constituents and their biological activities are unknown. OBJECTIVE: Isolation and identification of the compounds in the leaves and stems of M. sirikitiae and determination of their cytotoxicity. MATERIALS AND METHODS: Methanol extracts of the leaves and stems of M. sirikitiae were separated by chromatography, and spectroscopic methods were used to determine the structures of the components. The cytotoxicity of the extracts and pure compounds was evaluated using the sulforhodamine B assay with several cell lines. The cells were treated with the compounds at concentrations of 0.16–20 µg/mL for 48 or 72 h. RESULTS: The investigation of the extracts of M. sirikitiae leaves and stems resulted in the isolation of a new lignan, mitrephoran, and 15 known compounds. Among these compounds, 2-(3,4-dimethoxyphenyl)-6-(3,5-dimethoxyphenyl)-3,7-dioxabicyclo[3.3.0]octane, ciliaric acid, 6-methoxymarcanine A, and stepharanine were isolated from this genus for the first time. The alkaloids liriodenine and oxoputerine exhibited strong cytotoxicity against all tested cells (IC(50) values of 6.59–11.02 µM). In contrast, magnone A, 3′,4-O-dimethylcedrusin, and 6-methoxymarcanine A inhibited the growth of some of the tested cells (IC(50) values of 2.03–19.73 µM). Magnone A and 6-methoxymarcanine A showed low toxicity for Hek 293 cells (IC(50) >20 µM). DISCUSSION AND CONCLUSIONS: M. sirikitiae is a source of cytotoxic lignans and alkaloids. Among the cytotoxic compounds, magnone A and 6-methoxymarcanine A are potentially useful lead compounds for the further development of anticancer agents because of their selective inhibitory effects on cancer cell lines.