Lissoclinotoxins E and F, novel cytotoxic alkaloids from a Philippine didemnid ascidian

• Published in: Tetrahedron Vol. 59; no. 16; pp. 2855 - 2859
• Main Authors: Davis, Rohan A, Sandoval, Imelda T, Concepcion, Gisela P, Moreira da Rocha, Rosana, Ireland, Chris M
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 14.04.2003; Elsevier
• Subjects: alkaloids; ascidian; Chemistry; Chemistry, Organic; computational chemistry; cytotoxicity; didemnid; lissoclinotoxins E and F; MDA-MB-435S; MDA-MB-468; Physical Sciences; PTEN; Science & Technology; MDA-MB-435S; MDA-MB-468; alkaloids; didemnid; PTEN; lissoclinotoxins E and F; computational chemistry; cytotoxicity; ascidian; COLORIMETRIC ASSAY; MDA-MB-4355; TUMOR-SUPPRESSOR GENE; VARACIN; IDENTIFICATION; CANCER; BREAST; MMAC1; GROWTH; MUTATIONS
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/S0040-4020(03)00335-1

Bioassay-guided fractionation of the MeOH extract from a Philippine didemnid ascidian resulted in the isolation of two new dimeric alkaloids, lissoclinotoxins E ( 1 ) and F ( 2 ). The polysulfide structures for compounds 1 and 2 were determined by interpretation of spectroscopic data and chemical degradation. Computational chemistry studies suggested that the N-alkyl chains about the tricyclic systems of lissoclinotoxins E and F had trans and cis orientations, respectively. Alkaloids 1 and 2 displayed IC 50 values of 2.3 and 1.5 μg/mL, respectively, towards the PTEN-deficient human breast carcinoma cell line, MDA-MB-468. Bioassay-guided fractionation of the MeOH extract from a Philippine didemnid ascidian resulted in the isolation of two new dimeric alkaloids, lissoclinotoxins E ( 1 ) and F ( 2 ). The polysulfide structures for compounds 1 and 2 were determined by interpretation of spectroscopic data and chemical degradation. Alkaloids 1 and 2 displayed IC 50 values of 2.3 and 1.5 μg/mL, respectively, towards the PTEN-deficient human breast carcinoma cell line, MDA-MB-468.