Innovative Design and Synthesis of Antiparasitic Agents

The primary goal of this Phase I study was to test novel L-nucleoside compounds for their toxicity against the malaria parasite, Plasmodium falciparum. Preliminary investigations were also made, using selected compounds, to evaluate the transport and uptake of the infected erythrocyte and the metabolism of the compound by the parasite. L-nucleoside compounds suggested themselves for this application because of their low toxicity, which has been established in previously performed anticancer screens, both in vitro and in vivo, and their unique and selective ability to be transported into an infected erythrocyte The toxicity screens yielded several compounds with very promising activity. Since the compounds are practically non-toxic, it makes these results even more exciting The transport and metabolism tests indicated that the compounds were being taken up by the invaded cells and were being metabolized. The tests also indicated that healthy red blood cells did not take up the compounds, did not metabolize them and were unaffected by the toxicity that affected the parasitized cells.