In search of new cytotoxic derivatives based on the lupane scaffold, methyl betulonate and methyl 20,29-dihydrobetulonate were conjugated with Reformatsky reagents to provide homolupanes extended at the C3-carbon atom. Further transformations of the functional groups afforded a series of derivatives with 2-hydroxyethyl and allyl alcohol moieties. Their varying antiproliferative activity in vitro was then investigated in four cancer cell lines and in normal human BJ fibroblasts. In cervical carcinoma HeLa cells, derivatives 5, 6 and 17 were the most promising with lower micromolar IC50s and no toxicity to fibroblasts, thus showing a high therapeutic index. In addition, induction of apoptosis was found in HeLa cells after 24 h treatment with compounds 5, 6, 13 and 29. This newly synthesized series is more interesting than the published lupane and homolupane triterpenes and saponins, due to their nontoxicity towards healthy human cells and stronger cytotoxicity to various cancer cell lines. This approach increases their potential as anticancer agents.

Department of Experimental Biology Faculty of Science Palacký University Šlechtitelů 27 CZ 78371 Olomouc Czech Republic

Institute of Organic Chemistry Polish Academy of Sciences Kasprzaka 44 52 01 224 Warsaw Poland

Laboratory of Growth Regulators Institute of Experimental Botany of the Czech Academy of Sciences and Faculty of Science Palacký University Šlechtitelů 27 CZ 78371 Olomouc Czech Republic

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