Dr. Riscoe’s Experimental Chemotherapy laboratory focuses on the discovery, optimization and translational development of antiparasitic drugs, especially drugs for treatment and prevention of malaria, a severe and potentially fatal tropical disease. Using modern methods of drug design and chemical synthesis his laboratory has successfully created 5 novel antimalarial “chemotypes” with exemplary molecules in each category that are orally bioavailable and curative in mouse models of infection. The Portland VA and neighboring OHSU have filed for patent protection on all 5 chemotypes which include: 1) Dual functional acridones with blood stage activity that interact synergistically with many standard antimalarial agents, 2) 4-Aminoquinoline derivatives (“Pharmachins”), designed to replace chloroquine, that are rapidly active against multidrug resistant strains of Plasmodium falciparum parasites, 3) Quinolones (i.e., ELQ-300) that block parasite mitochondrial respiration and act vs. the blood, liver, gametocyte, and vector stages of parasite development, 4) Prodrugs of ELQ-300 for improved oral delivery and for injectable sustained-release and long-term protection against malaria, and 5) Biguanides with enhanced synergy in combination with anti-respiratory antimalarial drugs such as atovaquone and ELQ-300. It is noteworthy that ELQs (e.g., ELQ-316) are also potent against other parasites including Toxoplasma gondii and Babesia microti with proven activity demonstrated in vitro as well as in vivo. T. gondii is a eukaryotic intracellular parasite estimated to have infected billions of people worldwide, placing them at risk for toxoplasmosis. Fetuses and immune-compromised persons (e.g., HIV patients, transplant patients, and individuals undergoing cancer chemotherapy) are susceptible to severe toxoplasmosis, which can be fatal or lead to permanent ocular or neurologic disability. Even healthy people without immunodeficiency are susceptible to ocular disease which may cause vision loss. B. microti causes babesiosis which is transmitted by ticks. It is endemic in the New England region of the United States where it is called, “Nantucket Fever”. Like malaria and toxoplasmosis, babesiosis is a potentially fatal infection and new and effective drugs are urgently needed. It is noteworthy that B. microti is a common co-infection associated with Lyme disease and is regarded as the foremost infectious risk to the U.S. blood supply. The Portland VA’s Experimental Chemotherapy Lab also investigates drug mechanism of action by use of methods that are traditional to the fields of biochemistry, chemical biology and molecular parasitology. Dr. Riscoe’s laboratory receives support from the Department of Veterans Affairs, National Institutes of Health, and the Me...