| Research Abstract |
Previously, we have found that an acylated cholestane glycoside (XDSW-1) isolated from the bulbs of Ornithogalum saundersiae showed potent cytotoxic and cytostatic activities against various human malignant tumor cells. In a continuation, we evaluated cytotoxic activity of OSW-1 derivatives against HL-60 human leukemia cells and revealed the structure-activity relationships. The cytotoxicity of steroidal saponins were also examined. The results are as follows.
1) A total of 24 OSW-1 derivatives, 19 of which were isolated from the bulbs of O. saundersiae, O. thyrsoides, and Galtonia candicans, and 5 of which were chemically synthesized, were evaluated for their cytotoxic activity against HL-60 cells, leading to the new findings of the structure-activity relationships of the OSW-1 related compounds. The role of the acylated diglycoside group attached at C-16 of the aglycon for the appearance of the potent cytotoxicity has not been revealed, and we consider that the assignment of the role
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would finally lead the development of a new anticancer agent with new pharmacological mechanism.
2) Two new cholestane glycosides, named galtonioside A (1) and candicanosoide A (2), were isolated from G, candicans and their structures were formulated by spectroscopic and chemical methods. Compounds 1 and 2 showed strong cytotoxic activity against HL-60 cells, which was as potent as the clinically applied anticancer agents, etoposide and methotrexate. In the Jpn. Fdn. for Cancer Res. 38 cell line assay, 1 and 2 displayed differential cytotoxicities, with breast cancer, CNS cancer, and lung cancer subpanel cell lines showing particular sensitivity but with colon cancer, ovarian cancer, and stomach cancer subpanel cell lines being relatively resistant to them. The pattern of differential cytotoxicity of 1 and 2 was evaluated by Compare Program and was revealed not to be correlated with that shown by any of the other compounds including currently used anticancer drugs (correlation coefficient value is about 0.5). This indicates that 1 and 2 may have a unique mode of action and the potentiality as the leads of new anticancer agents.
3) The cytotoxic activities of the steroidal saponins mainly isolated from the Liliaceae plants against HL-60 cells were examined. Some steroidal saponins evaluated showed considerable cytotoxic activities, which were almost as potent as that of etoposide used as a positive control. The activities were found to be sensitive to the monosaccharides constituting the sugar moieties and their sequences, as well as to the structures of the aglycons. " Less
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