Efficacy of the tubercidin antileishmania action associated with an inhibitor of the nucleoside transport

Author(s)

Aoki, J. I. ^[1] ; Yamashiro-Kanashiro, E. H. ^[1] ; Ramos, D. C. C. ^[1] ; Cotrim, P. C. ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Trop Med, Dept Molestias Infecciosas & Parasitarias, BR-05403000 Sao Paulo - Brazil

• Document type: Journal article
• Source: Parasitology Research; v. 104, n. 2, p. 223-228, JAN 2009.
• Web of Science Citations: 5

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. (AU)