A series of triazole-containing novobiocin analogues has been designed, synthesized and their inhibitory activity determined. These compounds contain a triazole ring in lieu of the amide moiety present in the natural product. The anti-proliferative effects of these compounds were evaluated against two breast cancer cell lines (SKBr-3 and MCF-7), and manifested activities similar to their amide-containing counterparts. In addition, Hsp90-dependent client protein degradation was observed via western blot analysis, further supporting a common mode of Hsp90 inhibition for both structural classes.
Peterson, L. B., & Blagg, B. S. J. (2010). Click Chemistry to Probe Hsp90: Synthesis and Evaluation of a Series of Triazole Containing Novobiocin Analogues. Bioorganic & Medicinal Chemistry Letters, 20(13), 3957–3960. http://doi.org/10.1016/j.bmcl.2010.04.140