Development of Carprofen analogues with activity against Mycobacterium tuberculosis

Abstract

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.