Novel Triazole Hybrids of Betulin: Synthesis and Biological Activity Profile

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 <b>5a</b>-<b>k</b> and <b>6a</b>-<b>h</b> 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 <b>6b</b> 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 <b>5e</b> containing a 3'-deoxythymidine-5'-yl moiety exhibited antibacterial activity against two gram-negative bacteria vz. <i>Klebsiella</i><i>pneumoniae</i> and <i>Escherichia coli</i> (minimal inhibitory concentration (MIC) range of 0.95-1.95 μM).