In vivo and in vitro auranofin activity against Trypanosoma cruzi: Possible new uses for an old drug
Chagas disease, Sleeping Sickness, Nagana and Leishmaniasis are serious infections caused by protozoa of the order Kinetoplastidae. They were described over a century ago by seminal work of different physician-researchers and, despite the initial discoveries, few drugs have been made available for t...
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Veröffentlicht in: | Experimental parasitology 2016-07, Vol.166, p.189-193 |
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creator | da Silva, Marco Túlio Alves Silva-Jardim, Izaltina Portapilla, Gisele Bulhões de Lima, Gustavo Machado Alvares Costa, Fernanda Cristina Anibal, Fernanda de Freitas Thiemann, Otavio Henrique |
description | Chagas disease, Sleeping Sickness, Nagana and Leishmaniasis are serious infections caused by protozoa of the order Kinetoplastidae. They were described over a century ago by seminal work of different physician-researchers and, despite the initial discoveries, few drugs have been made available for the treatment of these infections. The drugs available present serious efficacy and toxicity problems. Moreover, the emergence of resistant strains has rendered the development of novel chemotherapeutic strategies a priority. Auranofin is currently in use to treat rheumatoid arthritis in humans. Previous reports showed that this compound presents activity against Trypanosoma brucei and Leishmania cells. In Trypanosoma cruzi cells, auranofin resulted in a more potent compound than benznidazole in vitro when tested in different DTUs. In vivo experiments, although not decreasing T. cruzi parasitemia, decreases host mortality. Therefore, we propose auranofin as a potential alternative for a new chemotherapy in Chagas disease with the added advantage of already being approved for use in humans.
[Display omitted]
•We tested the drug auranofin in Trypanosoma cruzi cells.•We show that auranofin is more potent than benznidazole.•We show the auranofin effect on the six Trypanosoma cruzi DTUs.•Auranofin is shown as a potential Trypanosoma cruzi drug. |
doi_str_mv | 10.1016/j.exppara.2015.05.012 |
format | Article |
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[Display omitted]
•We tested the drug auranofin in Trypanosoma cruzi cells.•We show that auranofin is more potent than benznidazole.•We show the auranofin effect on the six Trypanosoma cruzi DTUs.•Auranofin is shown as a potential Trypanosoma cruzi drug.</description><identifier>ISSN: 0014-4894</identifier><identifier>EISSN: 1090-2449</identifier><identifier>DOI: 10.1016/j.exppara.2015.05.012</identifier><identifier>PMID: 26183422</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Antirheumatic Agents - pharmacology ; Antirheumatic Agents - therapeutic use ; Auranofin ; Auranofin - pharmacology ; Auranofin - therapeutic use ; Cell Line ; Chagas Disease - drug therapy ; Chagas Disease - parasitology ; Chemotherapy ; Female ; Fibroblasts - parasitology ; Humans ; Inhibitory Concentration 50 ; Leishmania ; Lethal Dose 50 ; Mice ; Mice, Inbred BALB C ; Nitroimidazoles - pharmacology ; Parasitemia - drug therapy ; Parasitemia - parasitology ; Random Allocation ; Specific Pathogen-Free Organisms ; Trypanocidal Agents - pharmacology ; Trypanocidal Agents - therapeutic use ; Trypanosoma brucei ; Trypanosoma cruzi ; Trypanosoma cruzi - drug effects</subject><ispartof>Experimental parasitology, 2016-07, Vol.166, p.189-193</ispartof><rights>2015 Elsevier Inc.</rights><rights>Copyright © 2015 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c464t-c84647711165630d61b0225bb2788bc38025c5ec465a75318c2f90cd608e2c5b3</citedby><cites>FETCH-LOGICAL-c464t-c84647711165630d61b0225bb2788bc38025c5ec465a75318c2f90cd608e2c5b3</cites><orcidid>0000-0001-7108-3278</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.exppara.2015.05.012$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,778,782,3539,27911,27912,45982</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26183422$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>da Silva, Marco Túlio Alves</creatorcontrib><creatorcontrib>Silva-Jardim, Izaltina</creatorcontrib><creatorcontrib>Portapilla, Gisele Bulhões</creatorcontrib><creatorcontrib>de Lima, Gustavo Machado Alvares</creatorcontrib><creatorcontrib>Costa, Fernanda Cristina</creatorcontrib><creatorcontrib>Anibal, Fernanda de Freitas</creatorcontrib><creatorcontrib>Thiemann, Otavio Henrique</creatorcontrib><title>In vivo and in vitro auranofin activity against Trypanosoma cruzi: Possible new uses for an old drug</title><title>Experimental parasitology</title><addtitle>Exp Parasitol</addtitle><description>Chagas disease, Sleeping Sickness, Nagana and Leishmaniasis are serious infections caused by protozoa of the order Kinetoplastidae. They were described over a century ago by seminal work of different physician-researchers and, despite the initial discoveries, few drugs have been made available for the treatment of these infections. The drugs available present serious efficacy and toxicity problems. Moreover, the emergence of resistant strains has rendered the development of novel chemotherapeutic strategies a priority. Auranofin is currently in use to treat rheumatoid arthritis in humans. Previous reports showed that this compound presents activity against Trypanosoma brucei and Leishmania cells. In Trypanosoma cruzi cells, auranofin resulted in a more potent compound than benznidazole in vitro when tested in different DTUs. In vivo experiments, although not decreasing T. cruzi parasitemia, decreases host mortality. Therefore, we propose auranofin as a potential alternative for a new chemotherapy in Chagas disease with the added advantage of already being approved for use in humans.
[Display omitted]
•We tested the drug auranofin in Trypanosoma cruzi cells.•We show that auranofin is more potent than benznidazole.•We show the auranofin effect on the six Trypanosoma cruzi DTUs.•Auranofin is shown as a potential Trypanosoma cruzi drug.</description><subject>Animals</subject><subject>Antirheumatic Agents - pharmacology</subject><subject>Antirheumatic Agents - therapeutic use</subject><subject>Auranofin</subject><subject>Auranofin - pharmacology</subject><subject>Auranofin - therapeutic use</subject><subject>Cell Line</subject><subject>Chagas Disease - drug therapy</subject><subject>Chagas Disease - parasitology</subject><subject>Chemotherapy</subject><subject>Female</subject><subject>Fibroblasts - parasitology</subject><subject>Humans</subject><subject>Inhibitory Concentration 50</subject><subject>Leishmania</subject><subject>Lethal Dose 50</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Nitroimidazoles - pharmacology</subject><subject>Parasitemia - drug therapy</subject><subject>Parasitemia - parasitology</subject><subject>Random Allocation</subject><subject>Specific Pathogen-Free Organisms</subject><subject>Trypanocidal Agents - pharmacology</subject><subject>Trypanocidal Agents - therapeutic use</subject><subject>Trypanosoma brucei</subject><subject>Trypanosoma cruzi</subject><subject>Trypanosoma cruzi - drug effects</subject><issn>0014-4894</issn><issn>1090-2449</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMFu1DAQQC1ERbeFT6DykUuWGcfOOlyqqmpLpUrlUM6W40wqr7JxaicL26_hW_iyuuzCFWmk0dhvZuzH2EeEJQJWn9dL-jmONtqlAFRLyIHiDVsg1FAIKeu3bAGAspC6lsfsJKU1AGgU8h07FhXqUgqxYN3t8PvX1m8Dt0PL_Z9iirmaox1C5wdu3eTz2Y7bR-uHNPGHuBvzXQoby12cn_0X_i2k5Jue-EA_-Jwo8S7EPJGHvuVtnB_fs6PO9ok-HPIp-3599XD5tbi7v7m9vLgrnKzkVDid02qFiJWqSmgrbEAI1TRipXXjSg1COUUZVnalStROdDW4tgJNwqmmPGWf9nPHGJ5mSpPZ-OSo7-1AYU4GNegqO1B1RtUedTG_PlJnxug3Nu4MgnlVbNbmoNi8KjaQA0XuOzusmJsNtf-6_jrNwPkeoPzRradokvM0OGp9JDeZNvj_rHgBY-KRDA</recordid><startdate>201607</startdate><enddate>201607</enddate><creator>da Silva, Marco Túlio Alves</creator><creator>Silva-Jardim, Izaltina</creator><creator>Portapilla, Gisele Bulhões</creator><creator>de Lima, Gustavo Machado Alvares</creator><creator>Costa, Fernanda Cristina</creator><creator>Anibal, Fernanda de Freitas</creator><creator>Thiemann, Otavio Henrique</creator><general>Elsevier Inc</general><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>C1K</scope><scope>F1W</scope><scope>H95</scope><scope>H97</scope><scope>L.G</scope><scope>M7N</scope><orcidid>https://orcid.org/0000-0001-7108-3278</orcidid></search><sort><creationdate>201607</creationdate><title>In vivo and in vitro auranofin activity against Trypanosoma cruzi: Possible new uses for an old drug</title><author>da Silva, Marco Túlio Alves ; 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[Display omitted]
•We tested the drug auranofin in Trypanosoma cruzi cells.•We show that auranofin is more potent than benznidazole.•We show the auranofin effect on the six Trypanosoma cruzi DTUs.•Auranofin is shown as a potential Trypanosoma cruzi drug.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26183422</pmid><doi>10.1016/j.exppara.2015.05.012</doi><tpages>5</tpages><orcidid>https://orcid.org/0000-0001-7108-3278</orcidid></addata></record> |
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subjects | Animals Antirheumatic Agents - pharmacology Antirheumatic Agents - therapeutic use Auranofin Auranofin - pharmacology Auranofin - therapeutic use Cell Line Chagas Disease - drug therapy Chagas Disease - parasitology Chemotherapy Female Fibroblasts - parasitology Humans Inhibitory Concentration 50 Leishmania Lethal Dose 50 Mice Mice, Inbred BALB C Nitroimidazoles - pharmacology Parasitemia - drug therapy Parasitemia - parasitology Random Allocation Specific Pathogen-Free Organisms Trypanocidal Agents - pharmacology Trypanocidal Agents - therapeutic use Trypanosoma brucei Trypanosoma cruzi Trypanosoma cruzi - drug effects |
title | In vivo and in vitro auranofin activity against Trypanosoma cruzi: Possible new uses for an old drug |
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