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. 2013 Apr 17;18(4):4526-43.
doi: 10.3390/molecules18044526.

Synthesis, structure and cytotoxic activity of new acetylenic derivatives of betulin

Stanisław Boryczka  1 , Ewa Bębenek, Joanna Wietrzyk, Katarzyna Kempińska, Maria Jastrzębska, Joachim Kusz, Maria Nowak
Affiliations

Synthesis, structure and cytotoxic activity of new acetylenic derivatives of betulin

Stanisław Boryczka et al. Molecules. .

Abstract

A new series of betulin derivatives containing one or two pharmacophores bearing an acetylenic and carbonyl function at the C-3 and/or C-28 positions has been synthesized and characterized by ¹H- and ¹³C-NMR, IR, MS and elemental analyses. The crystal structure of 28-O-propynoylbetulin was determined by X-ray structural analysis. All new compounds, as well as betulin, were tested in vitro for their antiproliferative activity against human SW707 colorectal, CCRF/CEM leukemia, T47D breast cancer, and against murine P388 leukemia and Balb3T3 normal fibroblasts cell lines. Most of the compounds showed better cytotoxicity than betulin and cisplatin used as reference agent. 28-O-Propynoylbetulin was the most potent derivative, being over 500 times more potent than betulin and about 100 times more cytotoxic than cisplatin against the human leukemia (CCRF/CEM) cell line, with an ID₅₀ value of 0.02 μg/mL.

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Figures

Figure 1
Figure 1
Structure of betulin (1) and betulinic acid (2).
Scheme 1
Scheme 1
Synthesis of acetylenic derivatives of betulin 3–6.
Scheme 2
Scheme 2
Synthesis of betulin derivatives 7 and 8.
Figure 2
Figure 2
Molecular structure with atomic numbering scheme of 28-O-propynoylbetulin – DMSO solvate 5a with displacement ellipsoids of 50% probability.
Figure 3
Figure 3
Proposed mesomeric structures of propynoyl pharmacophore of 28-O-propynoylbetulin (5a).
See this image and copyright information in PMC

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