Marine natural alkaloids as anticancer agents
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of 6.48 mM (TSU-Pr1), 6.49 mM (TSU-Pr1-B1), 3.55 mM (TSU-Pr1-B2) and 3.66 mM (5637), whereas Compound (64) showed cytotoxic effect on 5637 and TSU-Pr1-B2 cells at 10 mM, with cell growth inhibitions of 54% and 51% cells, respectively, but did not have any effect on TSU-Pr1-B1 cells at 10 mM.
1.3. Hexacyclic alkaloids The extracts of a deep violet sponge Dercitus sp. collected in the Bahamas yielded a hexacyclic alkaloid cyclodercitin (64). The sixth ring in cyclodercitin (64) is formally derived by cyclization of the 2-aminoethyl side chain to the acridine nitrogen, while the pyridine ring is substituted with an N-methyl group. Cyclodercitin (64) inhibited the proliferation of P-388 murine leukemia cells in vitro with IC50 value of 1.9 µM. Recently, stellettamine (65) was isolated from a deep water marine sponge Stelleta sp. [61]. The molecular formula, C20H14N4S was determined by high resolution FAB mass spectroscopy. The structure of the compound was established on the basis of 1H-13C correlation spectroscopy except the orientation of thiazole ring. Therefore complete structure of stellettamine (65) was determined by a single-crystal X-ray diffraction experiment.
1.4. Heptacyclic alkaloids Eilatin (66) is the only known heptacyclic pyridoacridine alkaloid of the marine origin [62]. Molecular formula of eilatin (66) was determined as C24H12N4 by high-resolution EIMS. 1H NMR spectrum showed only six aromatic protons that could agree with the common six protons of the benzodiazaphenanthroline system. The 13C NMR spectrum exhibited only 12 carbon lines (6 for monoprotonated carbons and 6 nonprotonated carbons). This suggests a symmetrical dimeric structure for eilatin (66). Various 2D NMR experiments such as 1H-13C correlations and a HETCOSY experiment were failed to deduce the structure and finally it was determined by a single-crystal X-ray analysis. Eilatin (66) was found to exhibit cytotoxic activity against HCT cell line with IC50 value of 5.3 µM.
N
N
S
N
N
N
N
N
S
N N NMe2
64
65
N
66