METHODS AND RESULTS:
As a part of our continuing work to find out bioactive lead molecules from marine invertebrates, the CHCl₃ fraction of the organic extract of the Red Sea sponge Theonella mirabilis showed cytotoxic activity in our primary screen. Bioassay-guided purification of the active fractions of the sponge's extract resulted in the isolation of two new glycerides, mirabolides A and B (1 and 2), together with the reported 4-methylene sterols, Conicasterol (3) and swinhosterol B (4). The structures of the compounds were assigned by interpretation of their 1D (1H, (13)C), 2D (COSY, HSQC, HMBC, ROESY) NMR spectral data and high-resolution mass determinations.
CONCLUSIONS:
Compounds 1-4 displayed marked cytotoxic activity against human breast adenocarcinoma cell line (MCF-7) with IC50 values of 16.4, 5.18, 6.23 and 3.0 μg/mL, respectively, compared to 5.4 μg/mL observed by doxorubicin as reference drug. |