Evaluation of DL-alpha-difluoromethylornithine against susceptible and drug-resistant Trypanosoma brucei brucei.
The antitrypanosomal activity of the ornithine decarboxylase inhibitor DL-alpha-difluoromethylornithine (DFMO, eflornithine) was tested in ten stocks and one clone of the hemoflagellate Trypanosoma brucei brucei in an in vitro system. They showed varying levels of susceptibility to DFMO, their IC50 (the concentration which inhibited growth by 50%) values ranging from 81-691 microM. Differences in DFMO susceptibility were also demonstrated in mice. Combinations of melarsonyl potassium (mel W; trimelarsan) and DFMO showed an additive effect in vitro in a mel W-susceptible and a mel W-resistant stock, but an antagonistic effect in a mel W- and DFMO-susceptible clone. Combinations of suramin and DFMO showed an antagonistic effect in vitro in a suramin-susceptible clone, but a potentiation in a suramin-resistant stock.
Zweygarth
E
E
Kenya Trypanosomiasis Research Institute (KETRI), Kikuyu.
Kaminsky
R
R
D000818:Animals; D001152:Arsenicals / Q000494:pharmacology / Q000627:therapeutic use; D003470:Culture Media; D004133:Diminazene / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D004336:Drug Antagonism; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D000518:Eflornithine / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D008297:Male; D051379:Mice; D010617:Phenanthridines / Q000494:pharmacology / Q000627:therapeutic use; D013498:Suramin / Q000494:pharmacology / Q000627:therapeutic use; D014344:Trypanocidal Agents / Q000494:pharmacology / Q000627:therapeutic use; D014346:Trypanosoma brucei brucei / Q000187:drug effects*; D014353:Trypanosomiasis, African / Q000188:drug therapy*
D001152:Arsenicals; D003470:Culture Media; D007106:Immune Sera; D010617:Phenanthridines; D014344:Trypanocidal Agents; C015980:melarsonic acid; D013498:Suramin; C000702:isometamidium chloride; C003915:diminazene aceturate; D004133:Diminazene; D000518:Eflornithine