Activity of tunicamycin against Trypanosoma brucei in vitro and in vivo.
Tunicamycin, a specific inhibitor of glycoprotein biosynthesis, was evaluated for activity and chemotherapeutic potential against Trypanosoma brucei in vitro and in vivo. The inhibition of parasite incorporation of two radiolabeled macromolecular precursors, [methyl-3H]thymidine and D-[2-3H]mannose, was measured in short-term (4-h) microcultures. Mannose incorporation was inhibited over the concentration range of 0.01 to 10.0 microgram/ml, reaching 60% at the latter level. Thymidine incorporation was not affected. In vivo experiments indicated that a single dose of 2.0 mg of tunicamycin per kg can cure or significantly increase the life-span of mice of three different strains, each infected with T. brucei.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005944:Glucosamine / Q000031:analogs & derivatives*; D008297:Male; D008358:Mannose / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008813:Mice, Inbred ICR; D051381:Rats; D011919:Rats, Inbred Strains; D013936:Thymidine / Q000378:metabolism; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000378:metabolism; D014353:Trypanosomiasis, African / Q000188:drug therapy*; D014415:Tunicamycin / Q000494:pharmacology* / Q000627:therapeutic use
D014415:Tunicamycin; D005944:Glucosamine; D008358:Mannose; D013936:Thymidine