Martin Liam T, Daniel Chris, Guldberg-Allen Marcus, Navaratnarajah Anushandan, Anselmi Silvia, Burova Tina-Maria D, Willcocks Sam, Hailes Helen C, Bhakta Sanjib
Department of Chemistry, University College London, 20 Gordon Street, London WC1H0AJ, UK; Institute of Structural and Molecular Biology, School of Natural Sciences, Birkbeck University of London, Malet Street, London WC1E 7HX, UK.
Institute of Structural and Molecular Biology, School of Natural Sciences, Birkbeck University of London, Malet Street, London WC1E 7HX, UK.
Bioorg Med Chem. 2025 Sep 1;127:118226. doi: 10.1016/j.bmc.2025.118226. Epub 2025 May 6.
Carprofen, a veterinary non-steroidal anti-inflammatory drug, has demonstrated bactericidal activity against Mycobacterium tuberculosis and the closely related model organism M. bovis BCG. Herein, we present the SAR-driven optimisation of three series of carbazole-based carprofen analogues for increased antimycobacterial potency and selectivity over the human monocyte-derived THP-1 cell line. An efficient synthetic route was employed to assemble a range of carprofen analogues which were then evaluated in whole-cell phenotypic assays to establish their activity against well-studied model organisms for M. tuberculosis. The most promising compound was further profiled against M. tuberculosis H37Rv, confirming the identification of a potent antitubercular carbazole with significantly enhanced therapeutic potential.
