In vitro and in vivo antimalarial evaluation of semi-synthetic derivatives of gomphostenin

A novel series of semi-synthetic gomphostenin derivatives (1 to 9) were prepared utilizing C-14 hydroxyl group for the first time and studied for their antimalarial properties. In vitro antiplasmodial activity was evaluated against both the chloroquine-sensitive and resistant strains of Plasmodium falciparum. Most of the compounds exhibited superior or comparable antiplasmodial activity compared to parent compound i.e. gomphostenin (GN). Based upon in vitro antiplasmodial activity, compounds with IC50 values less than 10 μM were selected for in vivo antiplasmodial evaluation against Plasmodium berghei infection in mice model. GN derivatives 3 and 5 were found to have curative activity with moderate chemosupression of 65% and 69% respectively at the dose level of 150 mg/kg/day.