ARTEMISININ ANALOGS FOR THE TREATMENT OF TOXOPLASMOSIS

TOXOPLASMOSIS IS A SERIOUS DISEASE IN CONGENITALLY INFECTED INFANTS AND IMMUNOCOMPROMISED PATIENTS. MILLIONS OF DOLLARS ARE NEEDED EACH YEAR TO CARE FOR VICTIMS OF CONGENITAL TOXOPLASMOSIS IN THE UNITED STATES ALONE, AND TOXOPLASMIC ENCEPHALITIS IS NOW THE MOST COMMONLYRECOGNIZED CAUSE OF OPPORTUNISTIC INFECTION OF THE CENTRAL NERVOUS SYSTEM IN PATIENTS WITH AIDS. TOXOPLASMA GONDII, A PARASITE WITH WORLDWIDE DISTRIBUTION, IS ALSO A PATHOGEN OF SIGNIFICANT ECONOMIC IMPORTANCE IN SHEEP AND SWINE WHERE IT CAUSES ABORTION. ARTEMISININ (QINGHAOSU) AND CERTAIN DERIVATIVES HAVE SHOWN SIGNIFICANT ANTIPARASITIC ACTIVITY FOR THE RELATED DISEASES OF MALARIA OR TOXOPLASMOSIS. EXPANDED EVALUATION OF OTHER FUNCTIONAL DERIVATIVES AND CORRELATION OF RESULTS TO PHARMACOLOGICAL FACTORS LEADING TO HIGH EFFICACY AND LOW TOXICITY IS A NECESSARY STEP TOWARD COMMERCIALIZATION OF AN EFFECTIVE AGENT. THE IMMEDIATERESEARCH WILL FOCUS ON FUNCTIONAL DERIVATIVES OF ARTEMISININ AT THE C-12 POSITION WHICH WILL BECHEMICALLY SYNTHESIZED AND EVALUATED FOR INHIBITION OF GROWTH OF TOXOPLASMA GONDII BY PUBLISHEDMETHODS. WE HAVE A SUPPLY OF ARTEMISININ ON-HAND FOR STARTING MATERIAL, HAVE SUCCESSFULLY SYNTHESIZED OTHER DERIVATIVES, HAVE PUBLISHED INHIBITION STUDIES ON T. GONDII, AND HAVE THE NECESSARY TECHNICAL BACKGROUND TO INTERPRET THE RESULTS AS PRECEDENCE FOR FURTHER RESEARCH AND COMMERCIALIZATION.