Cytotoxic Clerodane Diterpenoids and Their Hydrolysis Products from <em>Casearia nigrescens</em> from the Rainforest of Madagascar
Bioassay-guided fractionation of the cytotoxic leaf and flower extract of Casearia nigrescens led to the isolation of four new clerodane diterpenoids, designated caseanigrescens A–D (1–4). These compounds were subject to hydrolysis to dialdehydes when stored in CDCl3. The structures of compounds 1–4 were determined using 1D and 2D NMR spectroscopy. All four compounds showed moderate cytotoxicity to the A2780 human ovarian cancer cell line, with an IC50 range of 0.83–1.4 µM.
In our continuing search for bioactive molecules from the rainforests of Madagascar as part of an International Cooperative Biodiversity Group (ICBG) program,2 an extract of the leaves and flowers of Casearia nigrescens Tul. (Flacourtiaceae) showed moderate cytotoxicity against the A2780 human ovarian cancer cell line. This extract was selected for fractionation based on its cytotoxicity and the lack of phytochemical data for this species. The crude extract was purified by liquid–liquid partition, reversed phase chromatography, and reversed phase HPLC to yield the four new clerodane diterpenoids 1–4, designated caseanigrescens A–D. These compounds were subject to hydrolysis to dialdehydes when stored in CDCl3.
The genus Casearia is a member of the Saliciaceae. It consists of about 180 species and occurs throughout the tropics. Five species are found in Madagascar.34 The Flacourtiaceae family, and Casearia in particular, are well known for the production of clerodane diterpenoids.58 Such compounds have been reported to possess a wide range of biological activities including cytotoxic, antimalarial, antimycobacterial, DNA-damaging, trypanocidal, immunosuppressive, antifungal, and apoptosis inducing activity.57915C. nigrescens is known locally as Hazondrano.
Footnotes
Supporting Information Available:H and C NMR spectra for compounds 1–4 and 7; H NMR spectrum of compound 6. This material is available free of charge via the Internet at http://pubs.acs.org.
References and Notes
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