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Synthesis 2010(22): 3839-3848  
DOI: 10.1055/s-0030-1258293
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis and Evaluation of Biological Activity of the Quaternary Ammonium Salts of Lupane-, Oleanane-, and Ursane-Type Acids

David Biedermanna, Barbara Eignerovab,c, Marian Hajduchd, Jan Sarek*e
a Institute of Microbiology, Academy of Sciences of the Czech Republic, Centre of Biocatalysis and Biotransformations, Vídeňská 1083, 142 20 Prague, Czech Republic
b Department of Organic and Nuclear Chemistry, Faculty of Science, Charles University in Prague, Hlavova 8, 128 43 Prague 2, Czech Republic
c Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic
d Laboratory of Experimental Medicine, Department of Pediatrics, Faculty of Medicine, Palacky University in Olomouc, Puškinova 6, 775 20 Olomouc, Czech Republic
e Department of Organic Chemistry, Faculty of Science, Palacky University in Olomouc, 17. Listopadu 1192/12, 771 46 Olomouc, Czech Republic
Fax: +420(226)015452; e-Mail: jan.sarek@gmail.com;
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Publikationsverlauf

Received 6 May 2010
Publikationsdatum:
08. Oktober 2010 (online)

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Abstract

The anticancer properties of the derivatives of natural pentacyclic triterpenoids have received much attention recently. Here we present the preparation and the evaluation of the anticancer activity of a novel group of derivatives: quaternary ammonium esters. The esters were synthesized by quaternization of the respective 2-bromoethyl esters of betulinic, dihydrobetulinic, platanic, oleanolic, ursolic, and 3β-acetoxy-21-oxolup-18-en-28-oic acids with common low-molecular-weight tertiary amines, namely trimethylamine, triethylamine, pyridine, and triethanolamine. However, the desired quaternary salts were obtained only from trimethylamine, triethylamine, and pyridine. In case of the reaction with triethanol­amine the elimination of one of the 2-hydroxyethyl groups occurred and only tertiary amines were formed. Most of the prepared compounds showed significant in vitro cytotoxic activity on the CEM T-lymfoblastic leukaemia cell line. Three of the six selected compounds {2-(triethylammonio)ethyl 3β-hydroxylup-20(29)-en-28-oate bromide, 2-(triethylammonio)ethyl 3b-hydroxylupan-28-oate bromide and 2-[bis(2-hydroxyethyl)amino]ethyl 3β-hydroxylupan-28-oate] exhibited strong cytotoxic activity on a panel of ten cell lines, including drug resistant.

Key words

amines - esters - terpenoids - natural products - cytotoxicity screening

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