I am primarily interested in the early stages of drug discovery and development, including the discovery of natural products, synthesising libraries of natural product analogues, and identifying their mechanism of action. My PhD research is focused on two classes of marine-derived diterpenes, the anti-inflammatory fuscosides and an antitubercular agent called pseudopteroxazole.
The fuscosides are a family of anti-inflammatory glycosides isolated from the Caribbean gorgonian Eunicea fusca. These compounds display potent 5-lipoxygenase inhibition and inhibit PMA-induced edema in mouse models. As part of our interest in discovering anti-inflammatory agents, we have further investigated this coral for new compounds belonging to this class of natural products which led to the discovery of eunicidiol. We have also studied the structure-activity relationships of the fuscosides by synthesizing a library of glycoside analogues using glycosylation chemistry.
Pseudopteroxazole is an antitubercular marine natural product isolated from Pseudopterogorgia elisabethae. This compound is active against resistant strains of Mycobacterium tuberculosis and also targets non-replicating persistent subpopulations of mycobacteria. We are interested in identifying the mechanism of action of pseudopteroxazole using semisynthetic natural product-based probes, which will identify cell targets by affinity chromatography or photoaffinity labeling.
McCulloch, M.W.B.; Haltli, B.H.; Marchbank, D.H.; Kerr, R.G. Evaluation of pseudopteroxazole and pseudopterosin derivatives against Mycobacterium tuberculosis and other pathogens. Mar. Drugs 2012, 10, 1711-1728.
Marchbank, D.H.; Berrué, F.; Kerr, R.G. Eunicidiol, an anti-inflammatory dilophol diterpene from Eunicea fusca. J. Nat. Prod. 2012, 75, 1289-1293.
Marchbank, D.H.; Kerr, R.G. Semisynthesis of fuscoside B analogues and eunicosides, and analysis of anti-inflammatory activity. Tetrahedron 2011, 67, 3053-3061.