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, 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.
Cavalcanti
Danielle P
DP
Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Bloco G, subsolo, 21949-900, Rio de Janeiro, RJ, Brazil.
Fragoso
Stênio P
SP
Goldenberg
Samuel
S
de Souza
Wanderley
W
Motta
Maria Cristina M
MC
D000818:Animals; D004261:DNA Replication; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D018105:DNA, Kinetoplast / Q000378:metabolism / Q000648:ultrastructure*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D009268:Nalidixic Acid / Q000494:pharmacology; D009675:Novobiocin / Q000494:pharmacology; D021261:Parasitic Sensitivity Tests; D059005:Topoisomerase II Inhibitors; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014351:Trypanosomatina / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development
D018105:DNA, Kinetoplast; D004791:Enzyme Inhibitors; D059005:Topoisomerase II Inhibitors; D014344:Trypanocidal Agents; D009675:Novobiocin; D009268:Nalidixic Acid; D005047:Etoposide; D004250:DNA Topoisomerases, Type II