Planta Med 2012; 78 - PD178
DOI: 10.1055/s-0032-1320536

Investigating the anti-tubercular mechanism of action of pseudopteroxazole: An activity-based photolabeling approach

DH Marchbank 1, MWB McCulloch 2, B Haltli 2, DP Overy 2, RG Kerr 1, 2
  • 1Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, Prince Edward Island, C1A 4P3, Canada
  • 2Department of Chemistry, University of Prince Edward Island

Mycobacterium tuberculosis (MTB), the etiologic agent of tuberculosis disease, causes nearly two million deaths annually and has established a latent infection in one third of the human population.1 Pseudopteroxazole (Ptx), a diterpene isolated from the coral Pseudopterogorgia elisabethae,2 exhibits promising activity in a model of non-replicating persistent MTB and against several drug-resistant MTB strains.3,4 Considering the structural novelty of Ptx, as well as its efficacy against drug-resistant MTB strains, we hypothesize that Ptx may exert its activity through a unique mechanism of action (MoA). The aim of this research is to identify the MoA of Ptx by pursuing two complementary strategies. The mode of action of Ptx will be determined by measuring the incorporation of tritiated precursors into bacterial macromolecules. Meanwhile, the cellular target of Ptx will be identified using an activity-based photolabeling strategy by employing semisynthetic photoaffinity probes.

1) Barry, C.E.; et al. Nat. Rev. Microbiol. 2009, 7, 845. 2) Rodríguez, A.D.; et al. Org. Lett. 1999, 1, 527. 3) McCulloch, M.W.B.; et al., J. Nat. Prod. 2011, 74, 2250. 4) McCulloch, M.W.B.; Haltli, B.; Marchbank, D.H.; Kerr, R.G. Mar. Drugs 2012 [submitted].