Background: Malaria, caused predominantly by the parasite Plasmodium falciparum and transmitted by anopheline mosquitoes, is a debilitating and potentially fatal disease affecting millions of people worldwide. Although several antimalarial agents have been developed, rapid emergence and spread of drug-resistance has rendered many of them ineffective and is threatening to cause a global resurgence of this disease. Thus, an urgent need exists for developing novel drugs that can combat malaria more effectively.
Technology: Mark Hay, Elizabeth Stout, Amy Lane, Karine LeRoch, Julia Kubanek, and An-Shen Lin From the School of Biology at Georgia Tech have discovered a unique family of marine natural products that can provide promising leads for the treatment of malaria. Isolated from the Fijian red alga Callophycus serratus, these novel bromophycolide compounds and their semi-synthetic derivatives exhibit antimalarial activity in the low micromolar range (IC50 0.3-0.9 µM) against Plasmodium falciparum. Bromophycolide A, the most abundant member of this compound class, has similar inhibitory activity against both chloroquine-sensitive and resistant Plasmodium falciparum.
Like chloroquine, Bromophycolide A also suppresses parasite proliferation inside the host red blood cells by inhibiting crystallization of heme to form non-toxic hemozoin and yet does not appear to be targeted by the same parasite resistance mechanism as chloroquine. Despite its short in vivo half-life and susceptibility to liver metabolism, Bromophycolide A has low toxicity and good bioavailability, and is significantly active in a mouse malaria model. Thus, the unique structural scaffold of the bromophycolide compounds together with their specific mechanism of action and pharmacological properties make them attractive candidates for developing potent antimalarial drugs.
Potential Commercial Applications: Development of drug resistance and the absence of preventative vaccines have made the battle to treat malaria and control its spread very challenging. The compounds presented in this invention, with their previously unknown structures and unique mechanism of action, hold promise for the development of novel, more effective drugs against malaria.
Benefits / Advantages:
Novel antimalarial natural products isolated from marine red algae
Unique structural scaffold could lead to new class of antimalarial agents
Low micromolar antimalarial activity could be improved to develop more potent drugs
- Chloroquine-like mechanism of action but likely not targeted by same resistance mechanism