The effect of topoisomerase II inhibitors on the kinetoplast ultrastructure

Topoisomerases from trypanosomatids play key functions in the replication and organization of kinetoplast DNA (kDNA). Hence, they are considered as potential targets for anti-parasite drugs. In this paper, the effect of topoisomerase II inhibitors, such as nalidixic acid, novobiocin and etoposide, o...

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Veröffentlicht in:Parasitology research (1987) 2004-12, Vol.94 (6), p.439-448
Hauptverfasser: CAVALCANTI, Danielle P, FRAGOSO, Stenio P, GOLDENBERG, Samuel, DE SOUZA, Wanderley, MOTTA, Maria Cristina M
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container_issue 6
container_start_page 439
container_title Parasitology research (1987)
container_volume 94
creator CAVALCANTI, Danielle P
FRAGOSO, Stenio P
GOLDENBERG, Samuel
DE SOUZA, Wanderley
MOTTA, Maria Cristina M
description Topoisomerases from trypanosomatids play key functions in the replication and organization of kinetoplast DNA (kDNA). Hence, they are considered as potential targets for anti-parasite drugs. In this paper, the effect of topoisomerase II inhibitors, such as nalidixic acid, novobiocin and etoposide, on the ultrastructure of trypanosomatids that present distinct kDNA arrangements was evaluated. Prokaryotic topoisomerase II inhibitors were more effective on growth arrest and ultrastructure changes than etoposide, a eukaryotic topoisomerase II inhibitor. With the exception of novobiocin, drug concentrations which inhibited cell proliferation also promoted kinetoplast ultrastructure alterations, including the redistribution of topoisomerase II. The data reinforce the concept that prokaryotic topoisomerase II inhibitors may offer greater selectivity in drug therapy of trypanosomatid infections.
doi_str_mv 10.1007/s00436-004-1223-4
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Hence, they are considered as potential targets for anti-parasite drugs. In this paper, the effect of topoisomerase II inhibitors, such as nalidixic acid, novobiocin and etoposide, on the ultrastructure of trypanosomatids that present distinct kDNA arrangements was evaluated. Prokaryotic topoisomerase II inhibitors were more effective on growth arrest and ultrastructure changes than etoposide, a eukaryotic topoisomerase II inhibitor. With the exception of novobiocin, drug concentrations which inhibited cell proliferation also promoted kinetoplast ultrastructure alterations, including the redistribution of topoisomerase II. 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subjects Animals
Biological and medical sciences
DNA Replication
DNA Topoisomerases, Type II - metabolism
DNA, Kinetoplast - metabolism
DNA, Kinetoplast - ultrastructure
Enzyme Inhibitors - pharmacology
Etoposide - pharmacology
Fundamental and applied biological sciences. Psychology
General aspects
General aspects and techniques. Study of several systematic groups. Models
Invertebrates
Nalidixic Acid - pharmacology
Novobiocin - pharmacology
Parasitic Sensitivity Tests
Topoisomerase II Inhibitors
Trypanocidal Agents - pharmacology
Trypanosomatina - drug effects
Trypanosomatina - enzymology
Trypanosomatina - genetics
Trypanosomatina - growth & development
title The effect of topoisomerase II inhibitors on the kinetoplast ultrastructure
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