Effects of mesoionic xanthine analogs on Trypanosoma musculi development in mice.
Two derivatives of the mesoionic thiazolo[3,2-a]pyrimidine-5,7-diones 1 were prepared and examined for in vivo antiprotozoan activity to study structure-activity relationships that might lead us to more active derivatives. Mesoionic compounds 1A and 1B were inoculated into Swiss Webster male mice with Trypanosoma musculi infection. The effects were measured by studying parasite populations during the course of patent period (days 9 through 15 post-infection). The injection of 200 micrograms of compound 1A along with 5 x 10(4) trypanosomes affected the level of parasitemia at both the peak and during days 9 to 13 post infection. Experimental animals that received drug 1A prior to and after infection with T. musculi developed significantly lower parasitemia as compared to the control animals at the height of parasite populations (day 11 of observation). The group that received the drug simultaneously with trypanosome infection had significantly lower parasitemias on day 11 and 13 of infection compared to the controls. The injection of 200 micrograms of mesoionic compound 1B along with 5 x 10(4) trypanosomes resulted in lower parasitemic levels in the prior treated and post inoculated groups on days 9 and 13 post-infection. Swiss Webster male mice treated with the test drug, compound 1B, simultaneously with an inoculation of parasites developed significant resistance against infection on days 9 and 11 post-infection. This trend was reversed for the rest of the observation period.
Department of Life Sciences, Virginia State University, Petersburg 23806.
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D000818:Animals; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009941:Organomercury Compounds / Q000494:pharmacology*; D011744:Pyrimidinones / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014345:Trypanosoma / Q000187:drug effects; D014352:Trypanosomiasis / Q000188:drug therapy*
D009941:Organomercury Compounds; D011744:Pyrimidinones; D013844:Thiazoles; D014344:Trypanocidal Agents; C081616:6-chloromercury-8-ethylthiazolo(3,2-a)pyrimidine-5,7-dione; C081615:8-(4-chlorophenyl)thiazolo(3,2-a)pyrimidine-5,7-dione