Triterpene bidesmosides are considered as highly cytotoxic saponins, usually less toxic against normal cells than monodesmosides, and less haemolytic. Biological activity of the betulin-type bidesmosides, rarely found in Nature, and seldom prepared due to serious synthetic problems, is poorly recognized. We report herein a protocol for the preparation of disubstituted lupane saponins (betulin bidesmosides) by treatment of their benzoates with potassium carbonate in dichloromethane / methanol solution. Cytotoxicity of all compounds was tested in vitro for a series of cancer cell lines, as well as normal human skin BJ fibroblasts. Presence of l-rhamnose moiety is crucial for cytotoxicity of betulin bidesmosides. On the other hand, l-arabinose fragment connected to lupane C-3 carbon atom significantly decreases activity. Presented results clearly show that betulin bidesmosides have significant clinical potential as anticancer agents.
- MeSH
- antitumorózní látky chemická syntéza chemie farmakologie MeSH
- buněčné linie MeSH
- HeLa buňky MeSH
- lidé MeSH
- MFC-7 buňky MeSH
- nádory farmakoterapie MeSH
- rhamnosa analogy a deriváty chemická syntéza farmakologie MeSH
- triterpeny chemická syntéza chemie farmakologie MeSH
- viabilita buněk účinky léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
A series of lupane-type saponins bearing OSW-1 disaccharide unit as well as its regio- and stereoisomers were prepared and used for the structure-activity relationships (SAR) study. Unexpected preference for 1→4-linked regioisomers and an unusual inversion of the conformation of the sugar rings were noted. Cytotoxic activity of new lupane compounds was evaluated in vitro and revealed that some saponins exhibited an interesting bioactivity profile against human cancer cell lines. Influence of the protecting groups on the cytotoxicity was investigated. These results open the way to the synthesis of various lupane-type triterpene and saponin derivatives as potential anticancer compounds.
- MeSH
- antitumorózní látky chemická syntéza chemie farmakologie MeSH
- arabinosa chemie MeSH
- disacharidy chemická syntéza chemie farmakologie MeSH
- glykosylace MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- saponiny chemie MeSH
- stereoizomerie MeSH
- techniky syntetické chemie MeSH
- triterpeny chemie MeSH
- vodíková vazba MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
