The antiplasmodial, toxicity and pharmacokinetic properties of synthetic derivatives of the natural product Curcumin

Abstract

Malaria is the most devastating protozoal infection in humans. There is widespread resistance to existing antimalarial agents hence the need for new antimalarial drugs. Curcumin, a natural product isolated from Curcuma /ongaldomestica, was used as a scaffold for the synthesis of new compounds with antiplasmodial activity. Curcumin was selected because of its low toxicity and is commercially available at a low cost.. Derivatives of curcumin were designed to act against selected molecular targets in Plasmodium falciparum. It was hoped that the derivatives would have a better oral bioavailability and antiplasmodial activity than the parent compound. The derivatives were tested for in vitro antiplasmodial activity against the chloroquine sensitive (D10) and chloroquine resistant (K1) strains. In addition they were evaluated for their in vitro ability to inhibit the formation of beta- hematin which is the chemical equivalent of hemozoin which is responsible for the pathophysiological responses observed in malaria.