New lupane bidesmosides exhibiting strong cytotoxic activities in vitro

0531674 - ÚEB 2021 RIV US eng J - Článek v odborném periodiku
Korda, A. - Rárová, Lucie - Pakulski, Z. - Strnad, Miroslav - Oklešťková, Jana - Kuczynska, K. - Cmoch, P. - Gwardiak, K. - Karczewski, R.
New lupane bidesmosides exhibiting strong cytotoxic activities in vitro.
Bioorganic Chemistry. Roč. 100, JUL (2020), č. článku 103868. ISSN 0045-2068. E-ISSN 1090-2120
Grant CEP: GA ČR(CZ) GA20-25308S
Institucionální podpora: RVO:61389030
Klíčová slova: Betulin bidesmosides * Birch bark * Cytotoxic activity * Structure–activity relationship * Synthesis
Obor OECD: Medicinal chemistry
Impakt faktor: 5.275, rok: 2020
Způsob publikování: Open access
http://doi.org/10.1016/j.bioorg.2020.103868

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.
Trvalý link: http://hdl.handle.net/11104/0310291