Effect of nitrobenzylthioinosinate on the toxicity of tubercidin and ethidium against Trypanosoma gambiense.
The coadministration of tubercidin and ethidium to mice infected with Trypanosoma gambiense gave a better parasite clearance than either of the single drugs. The combination was also more toxic to the mice but the inclusion of nitrobenzylthioinosinate in the therapy significantly alleviated the toxicity of the drug combination. Nitrobenzylthioinosinate per se had no trypanocidal activity and did not affect the trypanocidal action of the drugs. The biochemical basis for the nitrobenzylthioinosinate action appears to be due to the reduction of access of the drugs to tissues or organs sensitive to the toxic drugs. The potential for the use of this compound with nucleoside analogue compounds in the therapy of African trypanosomiasis is suggested.
D000818:Animals; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004996:Ethidium / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D007288:Inosine / Q000031:analogs & derivatives*; D008297:Male; D051379:Mice; D012263:Ribonucleosides / Q000494:pharmacology*; D013868:Thioinosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D013873:Thionucleotides / Q000494:pharmacology* / Q000627:therapeutic use; D014347:Trypanosoma brucei gambiense / Q000187:drug effects* / Q000254:growth & development; D014353:Trypanosomiasis, African / Q000188:drug therapy / Q000469:parasitology*; D014372:Tubercidin / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity
D012263:Ribonucleosides; D013873:Thionucleotides; D013868:Thioinosine; D007288:Inosine; C028318:nitrobenzylthioinosine 5'-monophosphate; D004996:Ethidium; D014372:Tubercidin