Effect of the Metal Ion on the anti T. cruzi Activity and Mechanism of Action of 5-Nitrofuryl-Containing Thiosemicarbazone Metal Complexes
Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a major health problem worldwide. In this work, we report the development of palladium and platinum metal complexes with 5‐nitrofuryl‐containing thiosemicarbazones (L) as bioactive ligands against T. cruzi and PTA (1,3,5‐triaza‐7...
Gespeichert in:
| Veröffentlicht in: | European journal of inorganic chemistry 2014-09, Vol.2014 (27), p.4677-4689 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 4689 |
|---|---|
| container_issue | 27 |
| container_start_page | 4677 |
| container_title | European journal of inorganic chemistry |
| container_volume | 2014 |
| creator | Cipriani, Micaella Toloza, Jeannette Bradford, Lara Putzu, Eugenia Vieites, Marisol Curbelo, Estela Tomaz, Ana Isabel Garat, Beatriz Guerrero, Juan Gancheff, Jorge S. Maya, Juan Diego Olea Azar, Claudio Gambino, Dinorah Otero, Lucía |
| description | Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a major health problem worldwide. In this work, we report the development of palladium and platinum metal complexes with 5‐nitrofuryl‐containing thiosemicarbazones (L) as bioactive ligands against T. cruzi and PTA (1,3,5‐triaza‐7‐phosphaadamantane) as co‐ligand. Eight new complexes of the formula [MCl(L)(PTA)] with M = Pd or Pt were synthesized and fully characterized. Most complexes showed similar activities against T. cruzi to those of the corresponding free thiosemicarbazone ligands. No significant differences between palladium and platinum complexes were observed. Metal compounds with the phenylthiosemicarbazone derivative were the most active ones (IC50 = 9.84 ± 0.32 and 4.94 ± 0.24 μM for Pd2+ and Pt2+, respectively). The prepared complexes were not toxic on mammalian cells, showing selective indexes of more than 10–20. The ability of the complexes to be reduced in the parasite, which leads to toxic free radical species, was confirmed by the detection of OH· and nitroanion free radical species by ESR spectroscopy experiments. Gel electrophoresis and fluorescence experiments were consistent with an intercalating‐like mode of DNA interaction for the complexes, but DNA interaction does not seem to be the main mechanism of anti T. cruzi action for these compounds. The results obtained show that complexation of the bioactive ligands with the selected metals is a valid strategy to obtain improved metal‐based antiparasitic compounds.
Eight complexes of formula [MCl(L)(PTA)] (M = Pd or Pt, L = 5‐nitrofuryl‐containing thiosemicarbazone ligands, PTA = 1,3,5‐triaza‐7‐phosphaadamantane) were obtained. Most were active in vitro against T. cruzi. The mechanism involves bioreduction and formation of free radical species. All interact with DNA in an intercalative‐like manner, but this does not lead to their antichagasic activity. |
| doi_str_mv | 10.1002/ejic.201402614 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1904219686</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3963453121</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5614-c30bc3793a9c277338e5c84a023b548e69fde9613118e1b10448bc14c028d6b03</originalsourceid><addsrcrecordid>eNqFkU1v1DAQhiNEJUrhytkSFy7ZemLHsY9VWJZF_RJdhMTFcrwO6yWJF9uh3f4EfjWOFqqKSyVLtsbPM6PRm2VvAM8A4-LUbK2eFRgoLhjQZ9kxYCFyzHjxPL0poTkIyl9kL0PYYowJJuw4-z1vW6Mjci2KG4MuTFQdWroBpTMV1BAtWs2Q9uO9RWc62l827lN5nVi9UYMN_SRPP5PVojK_tNG7dvT7Lq_dEJUd7PAdrTbWBdNbrXyj7t3wb1jt-l1n7kx4lR21qgvm9d_7JPvyYb6qP-bnV4tlfXae6zLtlWuCG00qQZTQRVURwk2pOVW4IE1JuWGiXRvBgABwAw1gSnmjgWpc8DVrMDnJ3h367rz7OZoQZW-DNl2nBuPGIEFgWoBgnD2NMuBARYlJQt_-h27d6Ie0iISK8RQLCEjU7EBp70LwppU7b3vl9xKwnFKUU4ryIcUkiINwazuzf4KW80_L-rGbH1wborl7cJX_IVlFqlJ-vVzI94vrm4tvn29kSf4AfOiu0A</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1768014191</pqid></control><display><type>article</type><title>Effect of the Metal Ion on the anti T. cruzi Activity and Mechanism of Action of 5-Nitrofuryl-Containing Thiosemicarbazone Metal Complexes</title><source>Wiley Online Library Journals Frontfile Complete</source><creator>Cipriani, Micaella ; Toloza, Jeannette ; Bradford, Lara ; Putzu, Eugenia ; Vieites, Marisol ; Curbelo, Estela ; Tomaz, Ana Isabel ; Garat, Beatriz ; Guerrero, Juan ; Gancheff, Jorge S. ; Maya, Juan Diego ; Olea Azar, Claudio ; Gambino, Dinorah ; Otero, Lucía</creator><creatorcontrib>Cipriani, Micaella ; Toloza, Jeannette ; Bradford, Lara ; Putzu, Eugenia ; Vieites, Marisol ; Curbelo, Estela ; Tomaz, Ana Isabel ; Garat, Beatriz ; Guerrero, Juan ; Gancheff, Jorge S. ; Maya, Juan Diego ; Olea Azar, Claudio ; Gambino, Dinorah ; Otero, Lucía</creatorcontrib><description>Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a major health problem worldwide. In this work, we report the development of palladium and platinum metal complexes with 5‐nitrofuryl‐containing thiosemicarbazones (L) as bioactive ligands against T. cruzi and PTA (1,3,5‐triaza‐7‐phosphaadamantane) as co‐ligand. Eight new complexes of the formula [MCl(L)(PTA)] with M = Pd or Pt were synthesized and fully characterized. Most complexes showed similar activities against T. cruzi to those of the corresponding free thiosemicarbazone ligands. No significant differences between palladium and platinum complexes were observed. Metal compounds with the phenylthiosemicarbazone derivative were the most active ones (IC50 = 9.84 ± 0.32 and 4.94 ± 0.24 μM for Pd2+ and Pt2+, respectively). The prepared complexes were not toxic on mammalian cells, showing selective indexes of more than 10–20. The ability of the complexes to be reduced in the parasite, which leads to toxic free radical species, was confirmed by the detection of OH· and nitroanion free radical species by ESR spectroscopy experiments. Gel electrophoresis and fluorescence experiments were consistent with an intercalating‐like mode of DNA interaction for the complexes, but DNA interaction does not seem to be the main mechanism of anti T. cruzi action for these compounds. The results obtained show that complexation of the bioactive ligands with the selected metals is a valid strategy to obtain improved metal‐based antiparasitic compounds.
Eight complexes of formula [MCl(L)(PTA)] (M = Pd or Pt, L = 5‐nitrofuryl‐containing thiosemicarbazone ligands, PTA = 1,3,5‐triaza‐7‐phosphaadamantane) were obtained. Most were active in vitro against T. cruzi. The mechanism involves bioreduction and formation of free radical species. All interact with DNA in an intercalative‐like manner, but this does not lead to their antichagasic activity.</description><identifier>ISSN: 1434-1948</identifier><identifier>EISSN: 1099-0682</identifier><identifier>DOI: 10.1002/ejic.201402614</identifier><language>eng</language><publisher>Weinheim: WILEY-VCH Verlag</publisher><subject>Biocompatibility ; Coordination compounds ; Deoxyribonucleic acid ; DNA ; Drug design ; Free radicals ; Ligands ; Palladium ; Parasites ; Platinum ; Trypanosoma cruzi</subject><ispartof>European journal of inorganic chemistry, 2014-09, Vol.2014 (27), p.4677-4689</ispartof><rights>Copyright © 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><rights>Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5614-c30bc3793a9c277338e5c84a023b548e69fde9613118e1b10448bc14c028d6b03</citedby><cites>FETCH-LOGICAL-c5614-c30bc3793a9c277338e5c84a023b548e69fde9613118e1b10448bc14c028d6b03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fejic.201402614$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fejic.201402614$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids></links><search><creatorcontrib>Cipriani, Micaella</creatorcontrib><creatorcontrib>Toloza, Jeannette</creatorcontrib><creatorcontrib>Bradford, Lara</creatorcontrib><creatorcontrib>Putzu, Eugenia</creatorcontrib><creatorcontrib>Vieites, Marisol</creatorcontrib><creatorcontrib>Curbelo, Estela</creatorcontrib><creatorcontrib>Tomaz, Ana Isabel</creatorcontrib><creatorcontrib>Garat, Beatriz</creatorcontrib><creatorcontrib>Guerrero, Juan</creatorcontrib><creatorcontrib>Gancheff, Jorge S.</creatorcontrib><creatorcontrib>Maya, Juan Diego</creatorcontrib><creatorcontrib>Olea Azar, Claudio</creatorcontrib><creatorcontrib>Gambino, Dinorah</creatorcontrib><creatorcontrib>Otero, Lucía</creatorcontrib><title>Effect of the Metal Ion on the anti T. cruzi Activity and Mechanism of Action of 5-Nitrofuryl-Containing Thiosemicarbazone Metal Complexes</title><title>European journal of inorganic chemistry</title><addtitle>Eur. J. Inorg. Chem</addtitle><description>Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a major health problem worldwide. In this work, we report the development of palladium and platinum metal complexes with 5‐nitrofuryl‐containing thiosemicarbazones (L) as bioactive ligands against T. cruzi and PTA (1,3,5‐triaza‐7‐phosphaadamantane) as co‐ligand. Eight new complexes of the formula [MCl(L)(PTA)] with M = Pd or Pt were synthesized and fully characterized. Most complexes showed similar activities against T. cruzi to those of the corresponding free thiosemicarbazone ligands. No significant differences between palladium and platinum complexes were observed. Metal compounds with the phenylthiosemicarbazone derivative were the most active ones (IC50 = 9.84 ± 0.32 and 4.94 ± 0.24 μM for Pd2+ and Pt2+, respectively). The prepared complexes were not toxic on mammalian cells, showing selective indexes of more than 10–20. The ability of the complexes to be reduced in the parasite, which leads to toxic free radical species, was confirmed by the detection of OH· and nitroanion free radical species by ESR spectroscopy experiments. Gel electrophoresis and fluorescence experiments were consistent with an intercalating‐like mode of DNA interaction for the complexes, but DNA interaction does not seem to be the main mechanism of anti T. cruzi action for these compounds. The results obtained show that complexation of the bioactive ligands with the selected metals is a valid strategy to obtain improved metal‐based antiparasitic compounds.
Eight complexes of formula [MCl(L)(PTA)] (M = Pd or Pt, L = 5‐nitrofuryl‐containing thiosemicarbazone ligands, PTA = 1,3,5‐triaza‐7‐phosphaadamantane) were obtained. Most were active in vitro against T. cruzi. The mechanism involves bioreduction and formation of free radical species. All interact with DNA in an intercalative‐like manner, but this does not lead to their antichagasic activity.</description><subject>Biocompatibility</subject><subject>Coordination compounds</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Drug design</subject><subject>Free radicals</subject><subject>Ligands</subject><subject>Palladium</subject><subject>Parasites</subject><subject>Platinum</subject><subject>Trypanosoma cruzi</subject><issn>1434-1948</issn><issn>1099-0682</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><recordid>eNqFkU1v1DAQhiNEJUrhytkSFy7ZemLHsY9VWJZF_RJdhMTFcrwO6yWJF9uh3f4EfjWOFqqKSyVLtsbPM6PRm2VvAM8A4-LUbK2eFRgoLhjQZ9kxYCFyzHjxPL0poTkIyl9kL0PYYowJJuw4-z1vW6Mjci2KG4MuTFQdWroBpTMV1BAtWs2Q9uO9RWc62l827lN5nVi9UYMN_SRPP5PVojK_tNG7dvT7Lq_dEJUd7PAdrTbWBdNbrXyj7t3wb1jt-l1n7kx4lR21qgvm9d_7JPvyYb6qP-bnV4tlfXae6zLtlWuCG00qQZTQRVURwk2pOVW4IE1JuWGiXRvBgABwAw1gSnmjgWpc8DVrMDnJ3h367rz7OZoQZW-DNl2nBuPGIEFgWoBgnD2NMuBARYlJQt_-h27d6Ie0iISK8RQLCEjU7EBp70LwppU7b3vl9xKwnFKUU4ryIcUkiINwazuzf4KW80_L-rGbH1wborl7cJX_IVlFqlJ-vVzI94vrm4tvn29kSf4AfOiu0A</recordid><startdate>201409</startdate><enddate>201409</enddate><creator>Cipriani, Micaella</creator><creator>Toloza, Jeannette</creator><creator>Bradford, Lara</creator><creator>Putzu, Eugenia</creator><creator>Vieites, Marisol</creator><creator>Curbelo, Estela</creator><creator>Tomaz, Ana Isabel</creator><creator>Garat, Beatriz</creator><creator>Guerrero, Juan</creator><creator>Gancheff, Jorge S.</creator><creator>Maya, Juan Diego</creator><creator>Olea Azar, Claudio</creator><creator>Gambino, Dinorah</creator><creator>Otero, Lucía</creator><general>WILEY-VCH Verlag</general><general>WILEY‐VCH Verlag</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>L7M</scope><scope>C1K</scope><scope>F1W</scope><scope>H95</scope><scope>H97</scope><scope>L.G</scope></search><sort><creationdate>201409</creationdate><title>Effect of the Metal Ion on the anti T. cruzi Activity and Mechanism of Action of 5-Nitrofuryl-Containing Thiosemicarbazone Metal Complexes</title><author>Cipriani, Micaella ; Toloza, Jeannette ; Bradford, Lara ; Putzu, Eugenia ; Vieites, Marisol ; Curbelo, Estela ; Tomaz, Ana Isabel ; Garat, Beatriz ; Guerrero, Juan ; Gancheff, Jorge S. ; Maya, Juan Diego ; Olea Azar, Claudio ; Gambino, Dinorah ; Otero, Lucía</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5614-c30bc3793a9c277338e5c84a023b548e69fde9613118e1b10448bc14c028d6b03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Biocompatibility</topic><topic>Coordination compounds</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Drug design</topic><topic>Free radicals</topic><topic>Ligands</topic><topic>Palladium</topic><topic>Parasites</topic><topic>Platinum</topic><topic>Trypanosoma cruzi</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cipriani, Micaella</creatorcontrib><creatorcontrib>Toloza, Jeannette</creatorcontrib><creatorcontrib>Bradford, Lara</creatorcontrib><creatorcontrib>Putzu, Eugenia</creatorcontrib><creatorcontrib>Vieites, Marisol</creatorcontrib><creatorcontrib>Curbelo, Estela</creatorcontrib><creatorcontrib>Tomaz, Ana Isabel</creatorcontrib><creatorcontrib>Garat, Beatriz</creatorcontrib><creatorcontrib>Guerrero, Juan</creatorcontrib><creatorcontrib>Gancheff, Jorge S.</creatorcontrib><creatorcontrib>Maya, Juan Diego</creatorcontrib><creatorcontrib>Olea Azar, Claudio</creatorcontrib><creatorcontrib>Gambino, Dinorah</creatorcontrib><creatorcontrib>Otero, Lucía</creatorcontrib><collection>Istex</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><jtitle>European journal of inorganic chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cipriani, Micaella</au><au>Toloza, Jeannette</au><au>Bradford, Lara</au><au>Putzu, Eugenia</au><au>Vieites, Marisol</au><au>Curbelo, Estela</au><au>Tomaz, Ana Isabel</au><au>Garat, Beatriz</au><au>Guerrero, Juan</au><au>Gancheff, Jorge S.</au><au>Maya, Juan Diego</au><au>Olea Azar, Claudio</au><au>Gambino, Dinorah</au><au>Otero, Lucía</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of the Metal Ion on the anti T. cruzi Activity and Mechanism of Action of 5-Nitrofuryl-Containing Thiosemicarbazone Metal Complexes</atitle><jtitle>European journal of inorganic chemistry</jtitle><addtitle>Eur. J. Inorg. Chem</addtitle><date>2014-09</date><risdate>2014</risdate><volume>2014</volume><issue>27</issue><spage>4677</spage><epage>4689</epage><pages>4677-4689</pages><issn>1434-1948</issn><eissn>1099-0682</eissn><abstract>Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a major health problem worldwide. In this work, we report the development of palladium and platinum metal complexes with 5‐nitrofuryl‐containing thiosemicarbazones (L) as bioactive ligands against T. cruzi and PTA (1,3,5‐triaza‐7‐phosphaadamantane) as co‐ligand. Eight new complexes of the formula [MCl(L)(PTA)] with M = Pd or Pt were synthesized and fully characterized. Most complexes showed similar activities against T. cruzi to those of the corresponding free thiosemicarbazone ligands. No significant differences between palladium and platinum complexes were observed. Metal compounds with the phenylthiosemicarbazone derivative were the most active ones (IC50 = 9.84 ± 0.32 and 4.94 ± 0.24 μM for Pd2+ and Pt2+, respectively). The prepared complexes were not toxic on mammalian cells, showing selective indexes of more than 10–20. The ability of the complexes to be reduced in the parasite, which leads to toxic free radical species, was confirmed by the detection of OH· and nitroanion free radical species by ESR spectroscopy experiments. Gel electrophoresis and fluorescence experiments were consistent with an intercalating‐like mode of DNA interaction for the complexes, but DNA interaction does not seem to be the main mechanism of anti T. cruzi action for these compounds. The results obtained show that complexation of the bioactive ligands with the selected metals is a valid strategy to obtain improved metal‐based antiparasitic compounds.
Eight complexes of formula [MCl(L)(PTA)] (M = Pd or Pt, L = 5‐nitrofuryl‐containing thiosemicarbazone ligands, PTA = 1,3,5‐triaza‐7‐phosphaadamantane) were obtained. Most were active in vitro against T. cruzi. The mechanism involves bioreduction and formation of free radical species. All interact with DNA in an intercalative‐like manner, but this does not lead to their antichagasic activity.</abstract><cop>Weinheim</cop><pub>WILEY-VCH Verlag</pub><doi>10.1002/ejic.201402614</doi><tpages>13</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1434-1948 |
| ispartof | European journal of inorganic chemistry, 2014-09, Vol.2014 (27), p.4677-4689 |
| issn | 1434-1948 1099-0682 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1904219686 |
| source | Wiley Online Library Journals Frontfile Complete |
| subjects | Biocompatibility Coordination compounds Deoxyribonucleic acid DNA Drug design Free radicals Ligands Palladium Parasites Platinum Trypanosoma cruzi |
| title | Effect of the Metal Ion on the anti T. cruzi Activity and Mechanism of Action of 5-Nitrofuryl-Containing Thiosemicarbazone Metal Complexes |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T03%3A03%3A03IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Effect%20of%20the%20Metal%20Ion%20on%20the%20anti%20T.%20cruzi%20Activity%20and%20Mechanism%20of%20Action%20of%205-Nitrofuryl-Containing%20Thiosemicarbazone%20Metal%20Complexes&rft.jtitle=European%20journal%20of%20inorganic%20chemistry&rft.au=Cipriani,%20Micaella&rft.date=2014-09&rft.volume=2014&rft.issue=27&rft.spage=4677&rft.epage=4689&rft.pages=4677-4689&rft.issn=1434-1948&rft.eissn=1099-0682&rft_id=info:doi/10.1002/ejic.201402614&rft_dat=%3Cproquest_cross%3E3963453121%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1768014191&rft_id=info:pmid/&rfr_iscdi=true |