Synthesis and Chemical−Pharmacological Characterization of the Antimetastatic NAMI-A-Type Ru(III) Complexes (Hdmtp)[trans-RuCl4(dmso-S)(dmtp)], (Na)[trans-RuCl4(dmso-S)(dmtp)], and [mer-RuCl3(H2O)(dmso-S)(dmtp)] (dmtp = 5,7-Dimethyl[1,2,4]triazolo[1,5-a]pyrimidine)
Ruthenium compounds have gained large interest for their potential application as chemotherapeutic agents, and in particular the complexes of the type (X)[trans-RuCl4(dmso-S)L] (X = HL or Na, NAMI-A or NAMI, respectively, for L = imidazole) are under investigation for their antimetastatic properties...
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| Veröffentlicht in: | Journal of medicinal chemistry 2004-02, Vol.47 (5), p.1110-1121 |
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| creator | Velders, Aldrik H Bergamo, Alberta Alessio, Enzo Zangrando, Ennio Haasnoot, Jaap G Casarsa, Claudia Cocchietto, Moreno Zorzet, Sonia Sava, Gianni |
| description | Ruthenium compounds have gained large interest for their potential application as chemotherapeutic agents, and in particular the complexes of the type (X)[trans-RuCl4(dmso-S)L] (X = HL or Na, NAMI-A or NAMI, respectively, for L = imidazole) are under investigation for their antimetastatic properties. The NAMI(-A)-like compounds are prodrugs that hydrolyze in vivo, and the investigation of their hydrolytic properties is therefore important for determining the nature of the potential active species. The NAMI-A-type Ru(III) complex 1, (Hdmtp)[trans-RuCl4(dmso-S)(dmtp)] (dmtp is 5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidine), and the corresponding sodium analogue 2, (Na)[trans-RuCl4(dmso-S)(dmtp)], were synthesized. The hydrolyses of 1 and 2 in water as well as in buffered solutions were studied, and the first hydrolysis product, [mer-RuCl3(H2O)(dmso-S)(dmtp)]·H2O (3), was isolated and characterized. The molecular structures of 1 and 3 were determined by single-crystal X-ray diffraction analyses and prove the importance of the hydrogen-bonding properties of dmtp to stabilize hydrolysis products. In vitro 1 (a) is not cytotoxic on tumor cells, following challenges from 1 to 72 h and concentrations up to 100 μM, (b) inhibits matrigel invasion at 0.1 mM and MMP-9 activity with an IC50 of about 1 mM, and (c) is devoid of pronounced effects on cell distribution among cell cycle phases. In vivo compound 1, similar to NAMI-A, significantly inhibits metastasis growth in mice bearing advanced MCa mammary carcinoma tumors. In the lungs, 1 is significantly less concentrated than NAMI-A, whereas no differences between these two compounds were found in other organs such as tumor, liver, and kidney. However, 1 caused edema and necrotic areas on liver parenchyma that are more pronounced than those caused by NAMI-A. Conversely, glomerular and tubular changes on kidney are less extensive than with NAMI-A. In conclusion, 1 confirms the excellent antimetastatic properties of this class of NAMI-A-type compounds and qualifies as an interesting alternative to NAMI-A for treating human cancers. |
| doi_str_mv | 10.1021/jm030984d |
| format | Article |
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The NAMI(-A)-like compounds are prodrugs that hydrolyze in vivo, and the investigation of their hydrolytic properties is therefore important for determining the nature of the potential active species. The NAMI-A-type Ru(III) complex 1, (Hdmtp)[trans-RuCl4(dmso-S)(dmtp)] (dmtp is 5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidine), and the corresponding sodium analogue 2, (Na)[trans-RuCl4(dmso-S)(dmtp)], were synthesized. The hydrolyses of 1 and 2 in water as well as in buffered solutions were studied, and the first hydrolysis product, [mer-RuCl3(H2O)(dmso-S)(dmtp)]·H2O (3), was isolated and characterized. The molecular structures of 1 and 3 were determined by single-crystal X-ray diffraction analyses and prove the importance of the hydrogen-bonding properties of dmtp to stabilize hydrolysis products. In vitro 1 (a) is not cytotoxic on tumor cells, following challenges from 1 to 72 h and concentrations up to 100 μM, (b) inhibits matrigel invasion at 0.1 mM and MMP-9 activity with an IC50 of about 1 mM, and (c) is devoid of pronounced effects on cell distribution among cell cycle phases. In vivo compound 1, similar to NAMI-A, significantly inhibits metastasis growth in mice bearing advanced MCa mammary carcinoma tumors. In the lungs, 1 is significantly less concentrated than NAMI-A, whereas no differences between these two compounds were found in other organs such as tumor, liver, and kidney. However, 1 caused edema and necrotic areas on liver parenchyma that are more pronounced than those caused by NAMI-A. Conversely, glomerular and tubular changes on kidney are less extensive than with NAMI-A. In conclusion, 1 confirms the excellent antimetastatic properties of this class of NAMI-A-type compounds and qualifies as an interesting alternative to NAMI-A for treating human cancers.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm030984d</identifier><identifier>PMID: 14971891</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Animals ; Antineoplastic agents ; Antineoplastic Agents - chemical synthesis ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Biological and medical sciences ; Cell Cycle - drug effects ; Cell Line, Tumor ; Cell Survival - drug effects ; Crystallography, X-Ray ; Drug Screening Assays, Antitumor ; General aspects ; Hydrolysis ; Kidney - drug effects ; Kidney - pathology ; Liver - drug effects ; Liver - pathology ; Lung Neoplasms - drug therapy ; Lung Neoplasms - secondary ; Magnetic Resonance Spectroscopy ; Mammary Neoplasms, Animal - pathology ; Matrix Metalloproteinase 9 - chemistry ; Medical sciences ; Mice ; Molecular Structure ; Neoplasm Invasiveness ; Neoplasm Metastasis - prevention & control ; Organometallic Compounds - chemical synthesis ; Organometallic Compounds - chemistry ; Organometallic Compounds - pharmacology ; Pharmacology. Drug treatments ; Ruthenium - pharmacokinetics ; Spectrophotometry, Ultraviolet ; Structure-Activity Relationship ; Tissue Distribution</subject><ispartof>Journal of medicinal chemistry, 2004-02, Vol.47 (5), p.1110-1121</ispartof><rights>Copyright © 2004 American Chemical Society</rights><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a379t-e018338e941f57da4cc2d1b981d63b29f8fbf9486fead8a9d41e787b0a5ff9b73</citedby><cites>FETCH-LOGICAL-a379t-e018338e941f57da4cc2d1b981d63b29f8fbf9486fead8a9d41e787b0a5ff9b73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jm030984d$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm030984d$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15489011$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14971891$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Velders, Aldrik H</creatorcontrib><creatorcontrib>Bergamo, Alberta</creatorcontrib><creatorcontrib>Alessio, Enzo</creatorcontrib><creatorcontrib>Zangrando, Ennio</creatorcontrib><creatorcontrib>Haasnoot, Jaap G</creatorcontrib><creatorcontrib>Casarsa, Claudia</creatorcontrib><creatorcontrib>Cocchietto, Moreno</creatorcontrib><creatorcontrib>Zorzet, Sonia</creatorcontrib><creatorcontrib>Sava, Gianni</creatorcontrib><title>Synthesis and Chemical−Pharmacological Characterization of the Antimetastatic NAMI-A-Type Ru(III) Complexes (Hdmtp)[trans-RuCl4(dmso-S)(dmtp)], (Na)[trans-RuCl4(dmso-S)(dmtp)], and [mer-RuCl3(H2O)(dmso-S)(dmtp)] (dmtp = 5,7-Dimethyl[1,2,4]triazolo[1,5-a]pyrimidine)</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>Ruthenium compounds have gained large interest for their potential application as chemotherapeutic agents, and in particular the complexes of the type (X)[trans-RuCl4(dmso-S)L] (X = HL or Na, NAMI-A or NAMI, respectively, for L = imidazole) are under investigation for their antimetastatic properties. The NAMI(-A)-like compounds are prodrugs that hydrolyze in vivo, and the investigation of their hydrolytic properties is therefore important for determining the nature of the potential active species. The NAMI-A-type Ru(III) complex 1, (Hdmtp)[trans-RuCl4(dmso-S)(dmtp)] (dmtp is 5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidine), and the corresponding sodium analogue 2, (Na)[trans-RuCl4(dmso-S)(dmtp)], were synthesized. The hydrolyses of 1 and 2 in water as well as in buffered solutions were studied, and the first hydrolysis product, [mer-RuCl3(H2O)(dmso-S)(dmtp)]·H2O (3), was isolated and characterized. The molecular structures of 1 and 3 were determined by single-crystal X-ray diffraction analyses and prove the importance of the hydrogen-bonding properties of dmtp to stabilize hydrolysis products. In vitro 1 (a) is not cytotoxic on tumor cells, following challenges from 1 to 72 h and concentrations up to 100 μM, (b) inhibits matrigel invasion at 0.1 mM and MMP-9 activity with an IC50 of about 1 mM, and (c) is devoid of pronounced effects on cell distribution among cell cycle phases. In vivo compound 1, similar to NAMI-A, significantly inhibits metastasis growth in mice bearing advanced MCa mammary carcinoma tumors. In the lungs, 1 is significantly less concentrated than NAMI-A, whereas no differences between these two compounds were found in other organs such as tumor, liver, and kidney. However, 1 caused edema and necrotic areas on liver parenchyma that are more pronounced than those caused by NAMI-A. Conversely, glomerular and tubular changes on kidney are less extensive than with NAMI-A. In conclusion, 1 confirms the excellent antimetastatic properties of this class of NAMI-A-type compounds and qualifies as an interesting alternative to NAMI-A for treating human cancers.</description><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Cell Cycle - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - drug effects</subject><subject>Crystallography, X-Ray</subject><subject>Drug Screening Assays, Antitumor</subject><subject>General aspects</subject><subject>Hydrolysis</subject><subject>Kidney - drug effects</subject><subject>Kidney - pathology</subject><subject>Liver - drug effects</subject><subject>Liver - pathology</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - secondary</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Mammary Neoplasms, Animal - pathology</subject><subject>Matrix Metalloproteinase 9 - chemistry</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Molecular Structure</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplasm Metastasis - prevention & control</subject><subject>Organometallic Compounds - chemical synthesis</subject><subject>Organometallic Compounds - chemistry</subject><subject>Organometallic Compounds - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Ruthenium - pharmacokinetics</subject><subject>Spectrophotometry, Ultraviolet</subject><subject>Structure-Activity Relationship</subject><subject>Tissue Distribution</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcuO0zAUhgMCMaWw4AWQN6BEqsFOnMZesKjKpYVhpkzLhqqKnMSeuuSG7UjTeQLWPCJPgnvRVEKI1ZHP__n49_k97xlGrzAK8etNhSLEKCnuez0chwgSisgDr4dQGMJwGEZn3mNjNgihCIfRI-8ME5ZgynDvXn--re1aGGUArwswXotK5bz8_fPXbM11xfOmbK53HSdxzXMrtLrlVjU1aCRwN8GotqoSlhvr2jm4GH2ewhFcbFsBrjp_Op0GYNxUbSluhAH-pKhsGyyt5rWBV924JH5RmQbOA3-vrAbAv-D_B3ZGl5XQeznyJ-Fl8BcD9hW8AfEggW939tbbcokH4YCsrFb81v3KHWPIV-1Wq0oVqhbBE--h5KURT4-17319_24xnsDzyw_T8egc8ihhFgqEaRRRwQiWcVJwkudhgTNGcTGMspBJKjPJCB1KwQvKWUGwSGiSIR5LybIk6nsvD3Nb3fzohLFppUwuypLXoulMShEeMure6HvBAcx1Y4wWMm2dWa63KUbpLvn0LnnHPj8O7bJKFCfyGLUDXhwBblye0i04V-bExYQyhHccPHDKWHFzp3P9PR0mURKni9k8_UjjL7Nv5FO6OM3luUk3Tadrt7t_GPwDer_QmA</recordid><startdate>20040226</startdate><enddate>20040226</enddate><creator>Velders, Aldrik H</creator><creator>Bergamo, Alberta</creator><creator>Alessio, Enzo</creator><creator>Zangrando, Ennio</creator><creator>Haasnoot, Jaap G</creator><creator>Casarsa, Claudia</creator><creator>Cocchietto, Moreno</creator><creator>Zorzet, Sonia</creator><creator>Sava, Gianni</creator><general>American Chemical Society</general><scope>BSCLL</scope><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>20040226</creationdate><title>Synthesis and Chemical−Pharmacological Characterization of the Antimetastatic NAMI-A-Type Ru(III) Complexes (Hdmtp)[trans-RuCl4(dmso-S)(dmtp)], (Na)[trans-RuCl4(dmso-S)(dmtp)], and [mer-RuCl3(H2O)(dmso-S)(dmtp)] (dmtp = 5,7-Dimethyl[1,2,4]triazolo[1,5-a]pyrimidine)</title><author>Velders, Aldrik H ; Bergamo, Alberta ; Alessio, Enzo ; Zangrando, Ennio ; Haasnoot, Jaap G ; Casarsa, Claudia ; Cocchietto, Moreno ; Zorzet, Sonia ; Sava, Gianni</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a379t-e018338e941f57da4cc2d1b981d63b29f8fbf9486fead8a9d41e787b0a5ff9b73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Cell Cycle - drug effects</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival - drug effects</topic><topic>Crystallography, X-Ray</topic><topic>Drug Screening Assays, Antitumor</topic><topic>General aspects</topic><topic>Hydrolysis</topic><topic>Kidney - drug effects</topic><topic>Kidney - pathology</topic><topic>Liver - drug effects</topic><topic>Liver - pathology</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - secondary</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Mammary Neoplasms, Animal - pathology</topic><topic>Matrix Metalloproteinase 9 - chemistry</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Molecular Structure</topic><topic>Neoplasm Invasiveness</topic><topic>Neoplasm Metastasis - prevention & control</topic><topic>Organometallic Compounds - chemical synthesis</topic><topic>Organometallic Compounds - chemistry</topic><topic>Organometallic Compounds - pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Ruthenium - pharmacokinetics</topic><topic>Spectrophotometry, Ultraviolet</topic><topic>Structure-Activity Relationship</topic><topic>Tissue Distribution</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Velders, Aldrik H</creatorcontrib><creatorcontrib>Bergamo, Alberta</creatorcontrib><creatorcontrib>Alessio, Enzo</creatorcontrib><creatorcontrib>Zangrando, Ennio</creatorcontrib><creatorcontrib>Haasnoot, Jaap G</creatorcontrib><creatorcontrib>Casarsa, Claudia</creatorcontrib><creatorcontrib>Cocchietto, Moreno</creatorcontrib><creatorcontrib>Zorzet, Sonia</creatorcontrib><creatorcontrib>Sava, Gianni</creatorcontrib><collection>Istex</collection><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>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Velders, Aldrik H</au><au>Bergamo, Alberta</au><au>Alessio, Enzo</au><au>Zangrando, Ennio</au><au>Haasnoot, Jaap G</au><au>Casarsa, Claudia</au><au>Cocchietto, Moreno</au><au>Zorzet, Sonia</au><au>Sava, Gianni</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis and Chemical−Pharmacological Characterization of the Antimetastatic NAMI-A-Type Ru(III) Complexes (Hdmtp)[trans-RuCl4(dmso-S)(dmtp)], (Na)[trans-RuCl4(dmso-S)(dmtp)], and [mer-RuCl3(H2O)(dmso-S)(dmtp)] (dmtp = 5,7-Dimethyl[1,2,4]triazolo[1,5-a]pyrimidine)</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>2004-02-26</date><risdate>2004</risdate><volume>47</volume><issue>5</issue><spage>1110</spage><epage>1121</epage><pages>1110-1121</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>Ruthenium compounds have gained large interest for their potential application as chemotherapeutic agents, and in particular the complexes of the type (X)[trans-RuCl4(dmso-S)L] (X = HL or Na, NAMI-A or NAMI, respectively, for L = imidazole) are under investigation for their antimetastatic properties. The NAMI(-A)-like compounds are prodrugs that hydrolyze in vivo, and the investigation of their hydrolytic properties is therefore important for determining the nature of the potential active species. The NAMI-A-type Ru(III) complex 1, (Hdmtp)[trans-RuCl4(dmso-S)(dmtp)] (dmtp is 5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidine), and the corresponding sodium analogue 2, (Na)[trans-RuCl4(dmso-S)(dmtp)], were synthesized. The hydrolyses of 1 and 2 in water as well as in buffered solutions were studied, and the first hydrolysis product, [mer-RuCl3(H2O)(dmso-S)(dmtp)]·H2O (3), was isolated and characterized. The molecular structures of 1 and 3 were determined by single-crystal X-ray diffraction analyses and prove the importance of the hydrogen-bonding properties of dmtp to stabilize hydrolysis products. In vitro 1 (a) is not cytotoxic on tumor cells, following challenges from 1 to 72 h and concentrations up to 100 μM, (b) inhibits matrigel invasion at 0.1 mM and MMP-9 activity with an IC50 of about 1 mM, and (c) is devoid of pronounced effects on cell distribution among cell cycle phases. In vivo compound 1, similar to NAMI-A, significantly inhibits metastasis growth in mice bearing advanced MCa mammary carcinoma tumors. In the lungs, 1 is significantly less concentrated than NAMI-A, whereas no differences between these two compounds were found in other organs such as tumor, liver, and kidney. However, 1 caused edema and necrotic areas on liver parenchyma that are more pronounced than those caused by NAMI-A. Conversely, glomerular and tubular changes on kidney are less extensive than with NAMI-A. In conclusion, 1 confirms the excellent antimetastatic properties of this class of NAMI-A-type compounds and qualifies as an interesting alternative to NAMI-A for treating human cancers.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>14971891</pmid><doi>10.1021/jm030984d</doi><tpages>12</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-2623 |
| ispartof | Journal of medicinal chemistry, 2004-02, Vol.47 (5), p.1110-1121 |
| issn | 0022-2623 1520-4804 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_80169883 |
| source | MEDLINE; American Chemical Society Journals |
| subjects | Animals Antineoplastic agents Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Biological and medical sciences Cell Cycle - drug effects Cell Line, Tumor Cell Survival - drug effects Crystallography, X-Ray Drug Screening Assays, Antitumor General aspects Hydrolysis Kidney - drug effects Kidney - pathology Liver - drug effects Liver - pathology Lung Neoplasms - drug therapy Lung Neoplasms - secondary Magnetic Resonance Spectroscopy Mammary Neoplasms, Animal - pathology Matrix Metalloproteinase 9 - chemistry Medical sciences Mice Molecular Structure Neoplasm Invasiveness Neoplasm Metastasis - prevention & control Organometallic Compounds - chemical synthesis Organometallic Compounds - chemistry Organometallic Compounds - pharmacology Pharmacology. Drug treatments Ruthenium - pharmacokinetics Spectrophotometry, Ultraviolet Structure-Activity Relationship Tissue Distribution |
| title | Synthesis and Chemical−Pharmacological Characterization of the Antimetastatic NAMI-A-Type Ru(III) Complexes (Hdmtp)[trans-RuCl4(dmso-S)(dmtp)], (Na)[trans-RuCl4(dmso-S)(dmtp)], and [mer-RuCl3(H2O)(dmso-S)(dmtp)] (dmtp = 5,7-Dimethyl[1,2,4]triazolo[1,5-a]pyrimidine) |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T09%3A47%3A33IST&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=Synthesis%20and%20Chemical%E2%88%92Pharmacological%20Characterization%20of%20the%20Antimetastatic%20NAMI-A-Type%20Ru(III)%20Complexes%20(Hdmtp)%5Btrans-RuCl4(dmso-S)(dmtp)%5D,%20(Na)%5Btrans-RuCl4(dmso-S)(dmtp)%5D,%20and%20%5Bmer-RuCl3(H2O)(dmso-S)(dmtp)%5D%20(dmtp%20=%205,7-Dimethyl%5B1,2,4%5Dtriazolo%5B1,5-a%5Dpyrimidine)&rft.jtitle=Journal%20of%20medicinal%20chemistry&rft.au=Velders,%20Aldrik%20H&rft.date=2004-02-26&rft.volume=47&rft.issue=5&rft.spage=1110&rft.epage=1121&rft.pages=1110-1121&rft.issn=0022-2623&rft.eissn=1520-4804&rft.coden=JMCMAR&rft_id=info:doi/10.1021/jm030984d&rft_dat=%3Cproquest_cross%3E80169883%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=80169883&rft_id=info:pmid/14971891&rfr_iscdi=true |