Haemolytic activity, cytotoxicity and membrane cell permeabilization of semi-synthetic and natural lupane- and oleanane-type saponins

Bioorg Med Chem. 2009 Mar 1;17(5):2002-8. doi: 10.1016/j.bmc.2009.01.022. Epub 2009 Jan 15.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Membrane Permeability / drug effects
  • Erythrocytes / metabolism
  • Hemolysis*
  • Humans
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / chemistry
  • Saponins / chemical synthesis
  • Saponins / chemistry
  • Saponins / toxicity*
  • Sheep
  • Triterpenes / chemistry*


  • Saponins
  • Triterpenes
  • oleanane
  • lupane
  • Oleanolic Acid