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 |
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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. The data reinforce the concept that prokaryotic topoisomerase II inhibitors may offer greater selectivity in drug therapy of trypanosomatid infections.</description><identifier>ISSN: 0932-0113</identifier><identifier>EISSN: 1432-1955</identifier><identifier>DOI: 10.1007/s00436-004-1223-4</identifier><identifier>PMID: 15517387</identifier><identifier>CODEN: PARREZ</identifier><language>eng</language><publisher>Berlin: Springer</publisher><subject>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</subject><ispartof>Parasitology research (1987), 2004-12, Vol.94 (6), p.439-448</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c329t-c1878b50b62f397ba7faf469f56c42ec280cf497b77fe1dbaa14229d603f9fdc3</citedby><cites>FETCH-LOGICAL-c329t-c1878b50b62f397ba7faf469f56c42ec280cf497b77fe1dbaa14229d603f9fdc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16348971$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15517387$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>CAVALCANTI, Danielle P</creatorcontrib><creatorcontrib>FRAGOSO, Stenio P</creatorcontrib><creatorcontrib>GOLDENBERG, Samuel</creatorcontrib><creatorcontrib>DE SOUZA, Wanderley</creatorcontrib><creatorcontrib>MOTTA, Maria Cristina M</creatorcontrib><title>The effect of topoisomerase II inhibitors on the kinetoplast ultrastructure</title><title>Parasitology research (1987)</title><addtitle>Parasitol Res</addtitle><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.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>DNA Replication</subject><subject>DNA Topoisomerases, Type II - metabolism</subject><subject>DNA, Kinetoplast - metabolism</subject><subject>DNA, Kinetoplast - ultrastructure</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Etoposide - pharmacology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>General aspects</subject><subject>General aspects and techniques. Study of several systematic groups. Models</subject><subject>Invertebrates</subject><subject>Nalidixic Acid - pharmacology</subject><subject>Novobiocin - pharmacology</subject><subject>Parasitic Sensitivity Tests</subject><subject>Topoisomerase II Inhibitors</subject><subject>Trypanocidal Agents - pharmacology</subject><subject>Trypanosomatina - drug effects</subject><subject>Trypanosomatina - enzymology</subject><subject>Trypanosomatina - genetics</subject><subject>Trypanosomatina - growth & development</subject><issn>0932-0113</issn><issn>1432-1955</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkM1OwzAQhC0EoqXwAFyQL3ALeG3HTo6o4qeiEpdythzHVgNpXGznwNvjqpF6mV1pvxlpB6FbII9AiHyKhHAmiqwFUMoKfobmwBktoC7LczQndd4JAJuhqxi_CQEpOL9EMyhLkKySc_Sx2VpsnbMmYe9w8nvfRb-zQUeLVyvcDduu6ZIPEfsBpwz_dIPNWK9jwmOfMpjCaNIY7DW6cLqP9maaC_T1-rJZvhfrz7fV8nldGEbrVBioZNWUpBHUsVo2WjrtuKhdKQyn1tCKGMfzQUpnoW20Bk5p3QrCXO1awxbo4Zi7D_53tDGpXReN7Xs9WD9GJSTk9yTLIBxBE3yMwTq1D91Ohz8FRB0aVMcGVVZ1aFDx7LmbwsdmZ9uTY6osA_cToKPRvQt6MF08cYLxqpbA_gGsKnnJ</recordid><startdate>20041201</startdate><enddate>20041201</enddate><creator>CAVALCANTI, Danielle P</creator><creator>FRAGOSO, Stenio P</creator><creator>GOLDENBERG, Samuel</creator><creator>DE SOUZA, Wanderley</creator><creator>MOTTA, Maria Cristina M</creator><general>Springer</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20041201</creationdate><title>The effect of topoisomerase II inhibitors on the kinetoplast ultrastructure</title><author>CAVALCANTI, Danielle P ; FRAGOSO, Stenio P ; GOLDENBERG, Samuel ; DE SOUZA, Wanderley ; MOTTA, Maria Cristina M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c329t-c1878b50b62f397ba7faf469f56c42ec280cf497b77fe1dbaa14229d603f9fdc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>DNA Replication</topic><topic>DNA Topoisomerases, Type II - metabolism</topic><topic>DNA, Kinetoplast - metabolism</topic><topic>DNA, Kinetoplast - ultrastructure</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Etoposide - pharmacology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>General aspects</topic><topic>General aspects and techniques. Study of several systematic groups. Models</topic><topic>Invertebrates</topic><topic>Nalidixic Acid - pharmacology</topic><topic>Novobiocin - pharmacology</topic><topic>Parasitic Sensitivity Tests</topic><topic>Topoisomerase II Inhibitors</topic><topic>Trypanocidal Agents - pharmacology</topic><topic>Trypanosomatina - drug effects</topic><topic>Trypanosomatina - enzymology</topic><topic>Trypanosomatina - genetics</topic><topic>Trypanosomatina - growth & development</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>CAVALCANTI, Danielle P</creatorcontrib><creatorcontrib>FRAGOSO, Stenio P</creatorcontrib><creatorcontrib>GOLDENBERG, Samuel</creatorcontrib><creatorcontrib>DE SOUZA, Wanderley</creatorcontrib><creatorcontrib>MOTTA, Maria Cristina M</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Parasitology research (1987)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>CAVALCANTI, Danielle P</au><au>FRAGOSO, Stenio P</au><au>GOLDENBERG, Samuel</au><au>DE SOUZA, Wanderley</au><au>MOTTA, Maria Cristina M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The effect of topoisomerase II inhibitors on the kinetoplast ultrastructure</atitle><jtitle>Parasitology research (1987)</jtitle><addtitle>Parasitol Res</addtitle><date>2004-12-01</date><risdate>2004</risdate><volume>94</volume><issue>6</issue><spage>439</spage><epage>448</epage><pages>439-448</pages><issn>0932-0113</issn><eissn>1432-1955</eissn><coden>PARREZ</coden><abstract>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.</abstract><cop>Berlin</cop><pub>Springer</pub><pmid>15517387</pmid><doi>10.1007/s00436-004-1223-4</doi><tpages>10</tpages></addata></record> |
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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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