Inhibition of hemoflagellates by camptothecin compounds

#1. Field of the Invention

#This invention relates to the inhibition of flagellated parasitic protozoa Trypanosoma and Leishmania with camptothecin compounds. Camptothecin compounds have the ring structure shown below. ##STR1## The invention also relates to the treatment of animals having hemoflagellate infections with camptothecin compounds.

#2. Background of the Invention

#Infective trypanosomes are introduced through the bite of the tsetse fly and multiply at the site of inoculation to cause swelling which then progresses to a trypanosoma chancre, spreading to lymph nodes, blood stream and in terminal stages to the central nervous system where it produces the typical symptoms of sleeping sickness including lethargy, lack of appetite, unconsciousness and possible death. In addition to sleeping sickness, trypanosome infection causes asymptomatic trypanosomiasis and Chagas' Disease. Chagas' Disease is contracted from reduviid bugs or from contaminated blood transfusions. Early symptoms include a local reaction at the site of inoculation, and generalized lymphadenopathy and hepatosplenomegaly. Chronic disease includes cardiomyopathy and arrhythmias, megaesophagus and megacolon. In the present invention, camptothecin and derivatives thereof have been found to effectively inhibit the trypanosomes responsible for these diseases.

#Specific trypanosomes which are inhibited by camptothecin compounds include T. brucei brucei, including T. brucei rhodensiense and T. brucei gambiense which are considered to be subspecies of T. brucei. Additional trypanosomes which may be treated with camptothecin compounds include T. equiperdum, T. cruzi the causative agent of Chagas' disease and T. rangeli which infects many children in South American countries.

#Infective Leishmania are introduced through the bite of an infected female phlebotomine sand fly. The infective form of Leishmania is called a metacyclic promastigote which is deposited in the skin when the sand fly bites. The organs primarily affected are the liver, spleen, bone marrow and the reticuloendothelial system. The spleen and liver become enlarged contributing to anemia and thrombocytopenia which are characteristic of visceral leishmaniasis. In the present invention, camptothecin and derivatives thereof have been found to effectively inhibit Leishmania hemoflagellates which are responsible for both cutaneous and visceral leishmaniasis.