Effect of C-ring modifications on the cytotoxicity of spirostan saponins and related glycosides
Twelve C-ring modified spirostanyl glycosides were synthesized and evaluated for their cytotoxicity against the human myeloid leukemia cell line (HL-60). With the aim of assessing the influence of the hydrophobic character, the conformational flexibility and the stereochemistry of the C-ring functionalities on the cytotoxic activity, a variety of spirostanic aglycones incorporating methylene, methoxyl, α,β-unsaturated ketone and lactone groups were subjected to a linear glycosylation strategy leading to glycosides derived from the 3,6-dipivaloylated β-d-glucoside and the β-chacotrioside moieties. The 3,6-dipivaloylated spirostanyl β-d-glucosides showed moderate to good cytotoxic activity against HL-60, but no significant cytotoxicity against benign blood cells. However, the cytotoxicity of spirostanyl β-chacotriosides was highly dependent on the nature of the C-ring functional groups of the steroidal aglycones. Actually, the chacotrioside-based saponins either with no functionality or bearing a hydrophobic methylene group at C-12 were the most cytotoxic ones against both HL-60 and benign blood cells. On the other hand, the incorporation of very polar functionalities and the opening of the ring C with the consequent loss of rigidity led to a significant drop in the cytotoxicity against HL-60. These results confirm that spirostanyl β-chacotriosides including very lipophilic aglycones are the most cytotoxic ones among their congeners.
| Main Authors: | , , , , , |
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| Other Authors: | |
| Format: | artículo biblioteca |
| Published: |
Elsevier
2012-07-12
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| Subjects: | Steroids, Saponins, Glycosides, Cytotoxicity, HL-60 cells, |
| Online Access: | http://hdl.handle.net/10261/199502 http://dx.doi.org/10.13039/501100004837 http://dx.doi.org/10.13039/501100000780 http://dx.doi.org/10.13039/501100003339 |
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