Planta Med 2013; 79 - CL8
DOI: 10.1055/s-0033-1348533

From Natural Products to Potential Drug Leads: Antimalarials from NZ Marine Organisms

J Wang 1, LPP Liew 1, AN Pearce 1, M Kaiser 2, BR Copp 1
  • 1The School of Chemical Sciences, University of Auckland, Auckland 1142, New Zealand
  • 2Swiss Tropical and Public Health Institute, CH-4002 Basel, Switzerland

Screening of synthesized and isolated marine natural products for in vitro activity against four parasitic protozoa identified the ascidian metabolites orthidine F (1), didemnidine B (2) and ascidiathiazone A (3) as being relatively non-toxic, moderate growth inhibitors of a dual drug-resistant strain of Plasmodium falciparum with IC50 0.89µM, 15.0 and 3.3µM, respectively. Extensive structure-activity relationship studies of the three compound classes yielded analogues with enhanced in vitro potency (IC50 low to sub-nanomolar) and selectivity. In vivo studies identified examples exhibiting ip and oral dosing activity towards P. berghei, highlighting their potential to act as antimalarial drug leads. The synthesis of the target compounds and biological data will be presented.