Haemolytic activity, cytotoxicity and membrane cell permeabilization of semi-synthetic and natural lupane- and oleanane-type saponins.
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| Abstract |
The haemolysis of red blood cells inducing toxicity in most animals including humans is a major drawback for the clinical development of saponins as antitumour agents. In this study, the haemolytic and cytotoxic activities as well as the membrane cell permeabilization property of a library of 31 semi-synthetic and natural lupane- and oleanane-type saponins were evaluated and the structure-activity relationships were established. It was shown that lupane-type saponins do not exhibit any haemolytic activity and membrane cell permeabilization property at the maximum concentration tested (100 microM) independently of the nature of the sugar moieties. While oleanane-type saponins such as beta-hederin (25) and hederacolchiside A(1) (27) cause the death of cancer cell lines by permeabilizing the cellular membranes, lupane-type saponins seem to proceed via another mechanism, which could be related to the induction of apoptosis. Altogether, the results indicate that the cytotoxic lupane-type glycosides 10 and 22 bearing an alpha-l-rhamnopyranose moiety at the C-3 position represent promising antitumour agents for further studies on tumour-bearing mice since they are devoid of toxicity associated with the haemolysis of red blood cells.
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| Authors | Charles Gauthier, Jean Legault, Karl Girard-Lalancette, Vakhtang Mshvildadze, André Pichette |
| Journal | Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 17 Issue 5 Pg. 2002-8 (Mar 01 2009) ISSN: 1464-3391 [Electronic] England |
| PMID | 19200744 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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