Novel Triazole Hybrids of Betulin: Synthesis and Biological Activity Profile

• Main Authors: Ewa Bębenek, Maria Jastrzębska, Monika Kadela-Tomanek, Elwira Chrobak, Beata Orzechowska, Katarzyna Zwolińska, Małgorzata Latocha, Anna Mertas, Zenon Czuba, Stanisław Boryczka
• Format: Article
• Language: English
• Published: MDPI AG 2017-11-01
• Series: Molecules
• Subjects: betulin; 1,3-dipolar cycloaddition; triazoles; antiviral activity; anticancer activity; antimicrobial activity
• Online Access: https://www.mdpi.com/1420-3049/22/11/1876

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. Klebsiella pneumoniae and Escherichia coli (minimal inhibitory concentration (MIC) range of 0.95–1.95 μM).