title: Efficacy of the tubercidin antileishmania action associated with an inhibitor of the nucleoside transport.
abstract: Tubercidin (TUB) is an adenosine analog with potent antiparasite action, unfortunately associated with severe host toxicity. Prevention of TUB toxicity can be reached associating nitrobenzylthioinosine (NBMPR), an inhibitor of the purine nucleoside transport, specifically target to the mammal cells. It was demonstrated that this nucleoside transport inhibitor has no significant effect in the in vitro uptake of TUB by Schistosoma mansoni and Trypanosoma gambiense. Seeking to evaluate if the association of these compounds is also effective against leishmania, we analyzed the TUB-NBMPR combined treatment in in vitro cultures of promastigote forms of Leishmania (L.) amazonensis, Leishmania (L.) chagasi, Leishmania (L.) major, and Leishmania (V.) braziliensis as well as in cultures of amastigote forms of L. (L.) amazonensis, mice macrophages infected with L. (L.) amazonensis, and in vivo tests in BALB/c mice infected with L. (L.) amazonensis. We demonstrated that TUB-NBMPR combined treatment can be effective against leishmania cells protecting mammalian cells from TUB toxicity.
authors.affiliation: Dept. Moléstias Infecciosas e Parasitárias, Instituto de Medicina Tropical, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 4704 degrees andar, São Paulo, SP 05403-000, Brazil.
authors.forename: J I
authors.initials: JI
authors.lastname: Aoki
authors.forename: E H
authors.initials: EH
authors.lastname: Yamashiro-Kanashiro
authors.forename: D C C
authors.initials: DC
authors.lastname: Ramos
authors.forename: P C
authors.initials: PC
authors.lastname: Cotrim
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D002478:Cells, Cultured; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D007891:Leishmania / Q000187:drug effects*; D007896:Leishmaniasis / Q000188:drug therapy*; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D012550:Schistosoma mansoni / Q000187:drug effects; D013868:Thioinosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D013873:Thionucleotides / Q000494:pharmacology / Q000627:therapeutic use*; D014347:Trypanosoma brucei gambiense / Q000187:drug effects; D014372:Tubercidin / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity
chemical_list: D000977:Antiparasitic Agents; D004791:Enzyme Inhibitors; D013873:Thionucleotides; D013868:Thioinosine; C028318:nitrobenzylthioinosine 5'-monophosphate; D014372:Tubercidin
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