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DOI: 10.1055/s-0033-1348533
From Natural Products to Potential Drug Leads: Antimalarials from NZ Marine Organisms
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.