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• W2112779964 endingPage "1995" @default.
• W2112779964 startingPage "1990" @default.
• W2112779964 abstract "ABSTRACT The emergence of Leishmania less sensitive to pentavalent antimonial agents (SbVs), the report of inhibition of purified topoisomerase I of Leishmania donovani by sodium stibogluconate (Pentostam), and the uncertain mechanism of action of antimonial drugs prompted an evaluation of SbVs in the stabilization of cleavable complexes in promastigotes of Leishmania ( Viannia ). The effect of camptothecin, an inhibitor of topoisomerase, and additive-free meglumine antimoniate (Glucantime) on the stabilization of cleavable DNA-protein complexes associated with the inhibition of topoisomerase was assessed in the human promonocytic cell line U-937, promastigotes of L. ( Viannia ) panamensis selected for SbV resistance in vitro, and the corresponding wild-type strain. The stabilization of cleavable complexes and the 50% effective dose (ED 50 ) of SbVs for parasites isolated from patients with relapses were also evaluated. The median ED 50 for the wild-type strain was 16.7 μg of SbV/ml, while that of the line selected for resistance was 209.5 μg of SbV/ml. Treatment with both meglumine antimoniate and sodium stibogluconate (20 to 200 μg of SbV/ml) stabilized DNA-protein complexes in the wild-type strain but not the resistant line. The ED 50 s of the SbVs for Leishmania strains from patients with relapses was comparable to those for the line selected for in vitro resistance, and DNA-protein complexes were not stabilized by exposure to meglumine antimoniate. Cleavable complexes were observed in all Leishmania strains treated with camptothecin. Camptothecin stabilized cleavable complexes in U-937 cells; SbVs did not. The selective effect of the SbVs on the stabilization of DNA-protein complexes in Leishmania and the loss of this effect in naturally resistant or experimentally derived SbV-resistant Leishmania suggest that topoisomerase may be a target of antimonial drugs." @default.
• W2112779964 created "2016-06-24" @default.
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• W2112779964 date "1998-08-01" @default.
• W2112779964 modified "2023-10-14" @default.
• W2112779964 title "Sensitivity of <i>Leishmania viannia panamensis</i> to Pentavalent Antimony Is Correlated with the Formation of Cleavable DNA-Protein Complexes" @default.
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• W2112779964 doi "https://doi.org/10.1128/aac.42.8.1990" @default.
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