Anti-tuberculosis activity and structure–activity relationships of oxygenated tricyclic carbazole alkaloids and synthetic derivatives

Publication date: 15 November 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 22
Author(s): Carsten Börger, Christian Brütting, Konstanze K. Julich-Gruner, Ronny Hesse, V. Pavan Kumar, Sebastian K. Kutz, Marika Rönnefahrt, Claudia Thomas, Baojie Wan, Scott G. Franzblau, Hans-Joachim Knölker
A series of 49 oxygenated tricyclic carbazole derivatives has been tested for inhibition of the growth of Mycobacterium tuberculosis and a mammalian cell line (vero cells). From this series, twelve carbazoles showed a significant anti-TB activity. The four most active compounds were the naturally occurring carbazole alkaloids clauszoline-M (45), murrayaline-C (41), carbalexin-C (27), and the synthetic carbazole derivative 22 with MIC90 values ranging from 1.5 to 3.7μM. The active compounds were virtually nontoxic for the mammalian cell line in the concentration range up to 50μM.

Graphical abstract

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