Synthesis, characterization, interaction with DNA and cytotoxicity of the new potential antitumour drug cis-K[Ru(eddp)Cl 2]
The new potential antitumour soluble drug K[Ru(eddp)Cl 2]·3H 2O, (eddp=ethylenediamine- N, N′-di-3-propionate) has been isolated and characterized. The analysis of the interaction of this complex with pBR322 plasmid DNA by circular dichroism spectroscopy shows that the ruthenium complex initially in...
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| Veröffentlicht in: | Journal of inorganic biochemistry 2003-10, Vol.97 (2), p.215-220 |
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| container_title | Journal of inorganic biochemistry |
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| creator | Grguric-Sipka, Sanja R Vilaplana, Rosario A Pérez, José M Fuertes, Miguel A Alonso, Carlos Alvarez, Ysmael Sabo, Tibor J González-Vı́lchez, Francisco |
| description | The new potential antitumour soluble drug K[Ru(eddp)Cl
2]·3H
2O, (eddp=ethylenediamine-
N,
N′-di-3-propionate) has been isolated and characterized. The analysis of the interaction of this complex with pBR322 plasmid DNA by circular dichroism spectroscopy shows that the ruthenium complex initially induces alteration of both CD positive and negative features resembling those previously observed for monofunctional platinum complexes. Further addition of drug at
r
i higher than 0.50 suggests appreciable conformational alterations of typical secondary structure of B-type DNA, implying loss of DNA helicity and unwinding of the double helix. The results reported herein about the binding of K[Ru(eddp)Cl
2] to the named plasmid performed by electrophoresis indicate that the Ru(III) center preferentially forms initial monofunctional adducts with this plasmid. In addition, the DNA binding data suggest that the plasmid is cleaved by K[Ru(eddp)Cl
2] in the presence of physiological concentrations of ascorbate. These results support the hypothesis that reactive Ru(II) species may be formed from Ru(III) upon incubation with a reductant agent such as ascorbate. The testing of the cytotoxic activity of this complex against several human cancer cell lines evidenced that K[Ru(eddp)Cl
2] complex had a remarkable and selective antiproliferative effect against the cervix carcinoma HeLa and colon adenocarcinoma HT-29, behaving in these two cases as an antineoplastic drug. |
| doi_str_mv | 10.1016/S0162-0134(03)00281-2 |
| format | Article |
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2]·3H
2O, (eddp=ethylenediamine-
N,
N′-di-3-propionate) has been isolated and characterized. The analysis of the interaction of this complex with pBR322 plasmid DNA by circular dichroism spectroscopy shows that the ruthenium complex initially induces alteration of both CD positive and negative features resembling those previously observed for monofunctional platinum complexes. Further addition of drug at
r
i higher than 0.50 suggests appreciable conformational alterations of typical secondary structure of B-type DNA, implying loss of DNA helicity and unwinding of the double helix. The results reported herein about the binding of K[Ru(eddp)Cl
2] to the named plasmid performed by electrophoresis indicate that the Ru(III) center preferentially forms initial monofunctional adducts with this plasmid. In addition, the DNA binding data suggest that the plasmid is cleaved by K[Ru(eddp)Cl
2] in the presence of physiological concentrations of ascorbate. These results support the hypothesis that reactive Ru(II) species may be formed from Ru(III) upon incubation with a reductant agent such as ascorbate. The testing of the cytotoxic activity of this complex against several human cancer cell lines evidenced that K[Ru(eddp)Cl
2] complex had a remarkable and selective antiproliferative effect against the cervix carcinoma HeLa and colon adenocarcinoma HT-29, behaving in these two cases as an antineoplastic drug.</description><identifier>ISSN: 0162-0134</identifier><identifier>EISSN: 1873-3344</identifier><identifier>DOI: 10.1016/S0162-0134(03)00281-2</identifier><identifier>PMID: 14512200</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Antineoplastic Agents - chemical synthesis ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Ascorbate ; Ascorbic Acid - chemistry ; Cell Division - drug effects ; Cell Line, Tumor ; Chromatography, Agarose ; Circular Dichroism ; Cytotoxicity ; DNA - chemistry ; Dose-Response Relationship, Drug ; Electrophoresis ; HeLa Cells ; HT29 Cells ; Humans ; Hydrolysis ; Intercalating Agents - chemical synthesis ; Intercalating Agents - chemistry ; Intercalating Agents - pharmacology ; Nucleic Acid Conformation - drug effects ; Organometallic Compounds - chemical synthesis ; Organometallic Compounds - chemistry ; Organometallic Compounds - pharmacology ; Oxidation-Reduction ; Plasmids - chemistry ; Ruthenium - chemistry ; Ruthenium complexes ; Spectrophotometry, Infrared ; Spectrophotometry, Ultraviolet</subject><ispartof>Journal of inorganic biochemistry, 2003-10, Vol.97 (2), p.215-220</ispartof><rights>2003 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c361t-e73d094d8648371eeb33ab2194f8d0c230ae3b94a56ec22a4f2619dab46d728b3</citedby><cites>FETCH-LOGICAL-c361t-e73d094d8648371eeb33ab2194f8d0c230ae3b94a56ec22a4f2619dab46d728b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0162013403002812$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14512200$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Grguric-Sipka, Sanja R</creatorcontrib><creatorcontrib>Vilaplana, Rosario A</creatorcontrib><creatorcontrib>Pérez, José M</creatorcontrib><creatorcontrib>Fuertes, Miguel A</creatorcontrib><creatorcontrib>Alonso, Carlos</creatorcontrib><creatorcontrib>Alvarez, Ysmael</creatorcontrib><creatorcontrib>Sabo, Tibor J</creatorcontrib><creatorcontrib>González-Vı́lchez, Francisco</creatorcontrib><title>Synthesis, characterization, interaction with DNA and cytotoxicity of the new potential antitumour drug cis-K[Ru(eddp)Cl 2]</title><title>Journal of inorganic biochemistry</title><addtitle>J Inorg Biochem</addtitle><description>The new potential antitumour soluble drug K[Ru(eddp)Cl
2]·3H
2O, (eddp=ethylenediamine-
N,
N′-di-3-propionate) has been isolated and characterized. The analysis of the interaction of this complex with pBR322 plasmid DNA by circular dichroism spectroscopy shows that the ruthenium complex initially induces alteration of both CD positive and negative features resembling those previously observed for monofunctional platinum complexes. Further addition of drug at
r
i higher than 0.50 suggests appreciable conformational alterations of typical secondary structure of B-type DNA, implying loss of DNA helicity and unwinding of the double helix. The results reported herein about the binding of K[Ru(eddp)Cl
2] to the named plasmid performed by electrophoresis indicate that the Ru(III) center preferentially forms initial monofunctional adducts with this plasmid. In addition, the DNA binding data suggest that the plasmid is cleaved by K[Ru(eddp)Cl
2] in the presence of physiological concentrations of ascorbate. These results support the hypothesis that reactive Ru(II) species may be formed from Ru(III) upon incubation with a reductant agent such as ascorbate. The testing of the cytotoxic activity of this complex against several human cancer cell lines evidenced that K[Ru(eddp)Cl
2] complex had a remarkable and selective antiproliferative effect against the cervix carcinoma HeLa and colon adenocarcinoma HT-29, behaving in these two cases as an antineoplastic drug.</description><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Ascorbate</subject><subject>Ascorbic Acid - chemistry</subject><subject>Cell Division - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Chromatography, Agarose</subject><subject>Circular Dichroism</subject><subject>Cytotoxicity</subject><subject>DNA - chemistry</subject><subject>Dose-Response Relationship, Drug</subject><subject>Electrophoresis</subject><subject>HeLa Cells</subject><subject>HT29 Cells</subject><subject>Humans</subject><subject>Hydrolysis</subject><subject>Intercalating Agents - chemical synthesis</subject><subject>Intercalating Agents - chemistry</subject><subject>Intercalating Agents - pharmacology</subject><subject>Nucleic Acid Conformation - drug effects</subject><subject>Organometallic Compounds - chemical synthesis</subject><subject>Organometallic Compounds - chemistry</subject><subject>Organometallic Compounds - pharmacology</subject><subject>Oxidation-Reduction</subject><subject>Plasmids - chemistry</subject><subject>Ruthenium - chemistry</subject><subject>Ruthenium complexes</subject><subject>Spectrophotometry, Infrared</subject><subject>Spectrophotometry, Ultraviolet</subject><issn>0162-0134</issn><issn>1873-3344</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtPGzEQgC1UBGnKTwD5hEDKUr_2dapQWqAqohKPU1VZXnuWGG3Wqe0thP55HBLBsZcZzeibGc2H0D4lJ5TQ4vNNCiwjlIsjwo8JYRXN2BYa0arkGedCfECjN2QXfQzhgRCS56LcQbtU5JQxQkbo382yjzMINkywnimvdARvn1W0rp9g26cqtVKBH22c4a9Xp1j1ButldNE9WW3jErsWpxW4h0e8cBH6aFWXqGjjMHeDx8YP91jbkP34dT0cgTGL42mH2e9PaLtVXYC9TR6ju7Nvt9OL7PLn-ffp6WWmeUFjBiU3pBamKkTFSwrQcK4aRmvRVoZoxokC3tRC5QVoxpRoWUFroxpRmJJVDR-jw_XehXd_BghRzm3Q0HWqBzcEWeYlq2vKEpivQe1dCB5aufB2rvxSUiJX1uWrdblSKgmXr9blau5gc2Bo5mDepzaaE_BlDUB6868FL4O20Gsw1oOO0jj7nxMvX3WSfQ</recordid><startdate>20031001</startdate><enddate>20031001</enddate><creator>Grguric-Sipka, Sanja R</creator><creator>Vilaplana, Rosario A</creator><creator>Pérez, José M</creator><creator>Fuertes, Miguel A</creator><creator>Alonso, Carlos</creator><creator>Alvarez, Ysmael</creator><creator>Sabo, Tibor J</creator><creator>González-Vı́lchez, Francisco</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>7X8</scope></search><sort><creationdate>20031001</creationdate><title>Synthesis, characterization, interaction with DNA and cytotoxicity of the new potential antitumour drug cis-K[Ru(eddp)Cl 2]</title><author>Grguric-Sipka, Sanja R ; Vilaplana, Rosario A ; Pérez, José M ; Fuertes, Miguel A ; Alonso, Carlos ; Alvarez, Ysmael ; Sabo, Tibor J ; González-Vı́lchez, Francisco</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c361t-e73d094d8648371eeb33ab2194f8d0c230ae3b94a56ec22a4f2619dab46d728b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Ascorbate</topic><topic>Ascorbic Acid - chemistry</topic><topic>Cell Division - drug effects</topic><topic>Cell Line, Tumor</topic><topic>Chromatography, Agarose</topic><topic>Circular Dichroism</topic><topic>Cytotoxicity</topic><topic>DNA - chemistry</topic><topic>Dose-Response Relationship, Drug</topic><topic>Electrophoresis</topic><topic>HeLa Cells</topic><topic>HT29 Cells</topic><topic>Humans</topic><topic>Hydrolysis</topic><topic>Intercalating Agents - chemical synthesis</topic><topic>Intercalating Agents - chemistry</topic><topic>Intercalating Agents - pharmacology</topic><topic>Nucleic Acid Conformation - drug effects</topic><topic>Organometallic Compounds - chemical synthesis</topic><topic>Organometallic Compounds - chemistry</topic><topic>Organometallic Compounds - pharmacology</topic><topic>Oxidation-Reduction</topic><topic>Plasmids - chemistry</topic><topic>Ruthenium - chemistry</topic><topic>Ruthenium complexes</topic><topic>Spectrophotometry, Infrared</topic><topic>Spectrophotometry, Ultraviolet</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Grguric-Sipka, Sanja R</creatorcontrib><creatorcontrib>Vilaplana, Rosario A</creatorcontrib><creatorcontrib>Pérez, José M</creatorcontrib><creatorcontrib>Fuertes, Miguel A</creatorcontrib><creatorcontrib>Alonso, Carlos</creatorcontrib><creatorcontrib>Alvarez, Ysmael</creatorcontrib><creatorcontrib>Sabo, Tibor J</creatorcontrib><creatorcontrib>González-Vı́lchez, Francisco</creatorcontrib><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>Journal of inorganic biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Grguric-Sipka, Sanja R</au><au>Vilaplana, Rosario A</au><au>Pérez, José M</au><au>Fuertes, Miguel A</au><au>Alonso, Carlos</au><au>Alvarez, Ysmael</au><au>Sabo, Tibor J</au><au>González-Vı́lchez, Francisco</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis, characterization, interaction with DNA and cytotoxicity of the new potential antitumour drug cis-K[Ru(eddp)Cl 2]</atitle><jtitle>Journal of inorganic biochemistry</jtitle><addtitle>J Inorg Biochem</addtitle><date>2003-10-01</date><risdate>2003</risdate><volume>97</volume><issue>2</issue><spage>215</spage><epage>220</epage><pages>215-220</pages><issn>0162-0134</issn><eissn>1873-3344</eissn><abstract>The new potential antitumour soluble drug K[Ru(eddp)Cl
2]·3H
2O, (eddp=ethylenediamine-
N,
N′-di-3-propionate) has been isolated and characterized. The analysis of the interaction of this complex with pBR322 plasmid DNA by circular dichroism spectroscopy shows that the ruthenium complex initially induces alteration of both CD positive and negative features resembling those previously observed for monofunctional platinum complexes. Further addition of drug at
r
i higher than 0.50 suggests appreciable conformational alterations of typical secondary structure of B-type DNA, implying loss of DNA helicity and unwinding of the double helix. The results reported herein about the binding of K[Ru(eddp)Cl
2] to the named plasmid performed by electrophoresis indicate that the Ru(III) center preferentially forms initial monofunctional adducts with this plasmid. In addition, the DNA binding data suggest that the plasmid is cleaved by K[Ru(eddp)Cl
2] in the presence of physiological concentrations of ascorbate. These results support the hypothesis that reactive Ru(II) species may be formed from Ru(III) upon incubation with a reductant agent such as ascorbate. The testing of the cytotoxic activity of this complex against several human cancer cell lines evidenced that K[Ru(eddp)Cl
2] complex had a remarkable and selective antiproliferative effect against the cervix carcinoma HeLa and colon adenocarcinoma HT-29, behaving in these two cases as an antineoplastic drug.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>14512200</pmid><doi>10.1016/S0162-0134(03)00281-2</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0162-0134 |
| ispartof | Journal of inorganic biochemistry, 2003-10, Vol.97 (2), p.215-220 |
| issn | 0162-0134 1873-3344 |
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| subjects | Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Ascorbate Ascorbic Acid - chemistry Cell Division - drug effects Cell Line, Tumor Chromatography, Agarose Circular Dichroism Cytotoxicity DNA - chemistry Dose-Response Relationship, Drug Electrophoresis HeLa Cells HT29 Cells Humans Hydrolysis Intercalating Agents - chemical synthesis Intercalating Agents - chemistry Intercalating Agents - pharmacology Nucleic Acid Conformation - drug effects Organometallic Compounds - chemical synthesis Organometallic Compounds - chemistry Organometallic Compounds - pharmacology Oxidation-Reduction Plasmids - chemistry Ruthenium - chemistry Ruthenium complexes Spectrophotometry, Infrared Spectrophotometry, Ultraviolet |
| title | Synthesis, characterization, interaction with DNA and cytotoxicity of the new potential antitumour drug cis-K[Ru(eddp)Cl 2] |
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