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. 2017 Nov 1;22(11):1876.
doi: 10.3390/molecules22111876.

Novel Triazole Hybrids of Betulin: Synthesis and Biological Activity Profile

Ewa Bębenek  1 , Maria Jastrzębska  2   3 , Monika Kadela-Tomanek  4 , Elwira Chrobak  5 , Beata Orzechowska  6 , Katarzyna Zwolińska  7 , Małgorzata Latocha  8 , Anna Mertas  9 , Zenon Czuba  10 , Stanisław Boryczka  11
Affiliations

Novel Triazole Hybrids of Betulin: Synthesis and Biological Activity Profile

Ewa Bębenek et al. Molecules. .

Abstract

Betulin derivatives containing a 1,2,3-triazole ring possess a wide spectrum of biological activities, including antiviral, anticancer, and antibacterial activity. A series of novel triazoles were prepared by the 1,3-dipolar cycloaddition reaction between the alkyne derivatives of betulin and organic azides. The chemical structures of the obtained compounds were defined by ¹H and 13C NMR, IR, and high-resolution mass spectrometry (HR-MS) analysis. The target triazoles were screened for their antiviral activity against DNA and RNA viruses. The cytotoxic activity of the obtained compounds 5a-k and 6a-h was determined using five human cancer cell lines (T47D, MCF-7, SNB-19, Colo-829, and C-32) by a WST-1 assay. The bistriazole 6b displayed a promising IC50 value (0.05 μM) against the human ductal carcinoma T47D (500-fold higher potency than cisplatin). The microdilution method was applied for an evaluation of the antimicrobial activity of all of the compounds. The triazole 5e containing a 3'-deoxythymidine-5'-yl moiety exhibited antibacterial activity against two gram-negative bacteria vz. Klebsiellapneumoniae and Escherichia coli (minimal inhibitory concentration (MIC) range of 0.95-1.95 μM).

Keywords: 1,3-dipolar cycloaddition; anticancer activity; antimicrobial activity; antiviral activity; betulin; triazoles.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structures of betulin 1 and betulinic acid 2.
Scheme 1
Scheme 1
Synthesis of the acetylenic 3–4 and triazole derivatives of betulin 5a–k and 6a–h.
Figure 2
Figure 2
Chemical structure of triazole 5a.
See this image and copyright information in PMC

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