Characterization of a versatile organometallic pro-drug (CORM) for experimental CO based therapeutics
The complex fac-[Mo(CO)(3)(histidinate)]Na has been reported to be an effective CO-Releasing Molecule in vivo, eliciting therapeutic effects in several animal models of disease. The CO releasing profile of this complex in different settings both in vitro and in vivo reveals that the compound can rea...
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| Veröffentlicht in: | Dalton transactions : an international journal of inorganic chemistry 2013-05, Vol.42 (17), p.5985-5998 |
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| container_title | Dalton transactions : an international journal of inorganic chemistry |
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| creator | Seixas, João D Mukhopadhyay, Abhik Santos-Silva, Teresa Otterbein, Leo E Gallo, David J Rodrigues, Sandra S Guerreiro, Bruno H Gonçalves, Ana M L Penacho, Nuno Marques, Ana R Coelho, Ana C Reis, Patrícia M Romão, Maria J Romão, Carlos C |
| description | The complex fac-[Mo(CO)(3)(histidinate)]Na has been reported to be an effective CO-Releasing Molecule in vivo, eliciting therapeutic effects in several animal models of disease. The CO releasing profile of this complex in different settings both in vitro and in vivo reveals that the compound can readily liberate all of its three CO equivalents under biological conditions. The compound has low toxicity and cytotoxicity and is not hemolytic. CO release is accompanied by a decrease in arterial blood pressure following administration in vivo. We studied its behavior in solution and upon the interaction with proteins. Reactive oxygen species (ROS) generation upon exposure to air and polyoxomolybdate formation in soaks with lysozyme crystals were observed as processes ensuing from the decomposition of the complex and the release of CO. |
| doi_str_mv | 10.1039/c2dt32174b |
| format | Article |
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The CO releasing profile of this complex in different settings both in vitro and in vivo reveals that the compound can readily liberate all of its three CO equivalents under biological conditions. The compound has low toxicity and cytotoxicity and is not hemolytic. CO release is accompanied by a decrease in arterial blood pressure following administration in vivo. We studied its behavior in solution and upon the interaction with proteins. 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The CO releasing profile of this complex in different settings both in vitro and in vivo reveals that the compound can readily liberate all of its three CO equivalents under biological conditions. The compound has low toxicity and cytotoxicity and is not hemolytic. CO release is accompanied by a decrease in arterial blood pressure following administration in vivo. We studied its behavior in solution and upon the interaction with proteins. Reactive oxygen species (ROS) generation upon exposure to air and polyoxomolybdate formation in soaks with lysozyme crystals were observed as processes ensuing from the decomposition of the complex and the release of CO.</description><subject>Animals</subject><subject>Binding Sites</subject><subject>Carbon Monoxide - metabolism</subject><subject>Cell Line</subject><subject>Cell Survival - drug effects</subject><subject>Coordination Complexes - chemical synthesis</subject><subject>Coordination Complexes - chemistry</subject><subject>Coordination Complexes - toxicity</subject><subject>Crystallography, X-Ray</subject><subject>Hemodynamics</subject><subject>Hemoglobins - chemistry</subject><subject>Hemoglobins - metabolism</subject><subject>Hemolysis</subject><subject>Hep G2 Cells</subject><subject>Humans</subject><subject>Mice</subject><subject>Muramidase - chemistry</subject><subject>Muramidase - metabolism</subject><subject>Organometallic Compounds - chemical synthesis</subject><subject>Organometallic Compounds - chemistry</subject><subject>Organometallic Compounds - toxicity</subject><subject>Prodrugs - chemical synthesis</subject><subject>Prodrugs - chemistry</subject><subject>Prodrugs - toxicity</subject><subject>Protein Structure, Tertiary</subject><subject>Serum Albumin - chemistry</subject><subject>Serum Albumin - metabolism</subject><issn>1477-9226</issn><issn>1477-9234</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUMtKA0EQHEQxMXrxA2SOKqzOK_u4CLo-IRKQeF56Z3qSlU1mmdkE9evdGA166m66qrq6CDnm7IIzmV1qYVopeKLKHdLnKkmiTEi1u-1F3CMHIbwxJgQbin3SE1IImcasTzCfgQfdoq8-oa3cgjpLga7Qh26skTo_hYWbYwt1XWnaeBcZv5zS03z88nxGrfMU35uOPsdFh6H5mJYQ0NB2hh4aXLaVDodkz0Id8OinDsjr_d0kf4xG44en_HoUaaVUG0FihsIYg5kVTCMoIbv_LJTMGCu1RYlZwlMsdcyNtMjitNTlMEkBTRybRA7I1Ua3WZZzNLqz5KEums4d-I_CQVX83yyqWTF1q0LGPFXZWuB8I6C9C8Gj3XI5K9ZhF7m4nXyHfdOBT_5e20J_05VfGnF-VA</recordid><startdate>20130507</startdate><enddate>20130507</enddate><creator>Seixas, João D</creator><creator>Mukhopadhyay, Abhik</creator><creator>Santos-Silva, Teresa</creator><creator>Otterbein, Leo E</creator><creator>Gallo, David J</creator><creator>Rodrigues, Sandra S</creator><creator>Guerreiro, Bruno H</creator><creator>Gonçalves, Ana M L</creator><creator>Penacho, Nuno</creator><creator>Marques, Ana R</creator><creator>Coelho, Ana C</creator><creator>Reis, Patrícia M</creator><creator>Romão, Maria J</creator><creator>Romão, Carlos C</creator><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>5PM</scope></search><sort><creationdate>20130507</creationdate><title>Characterization of a versatile organometallic pro-drug (CORM) for experimental CO based therapeutics</title><author>Seixas, João D ; Mukhopadhyay, Abhik ; Santos-Silva, Teresa ; Otterbein, Leo E ; Gallo, David J ; Rodrigues, Sandra S ; Guerreiro, Bruno H ; Gonçalves, Ana M L ; Penacho, Nuno ; Marques, Ana R ; Coelho, Ana C ; Reis, Patrícia M ; Romão, Maria J ; Romão, Carlos C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c444t-a7d52ddde9f20cea423039fab0ddf3cfe3e9718ebc61d3fe068bcb578aed66d73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Binding Sites</topic><topic>Carbon Monoxide - metabolism</topic><topic>Cell Line</topic><topic>Cell Survival - drug effects</topic><topic>Coordination Complexes - chemical synthesis</topic><topic>Coordination Complexes - chemistry</topic><topic>Coordination Complexes - toxicity</topic><topic>Crystallography, X-Ray</topic><topic>Hemodynamics</topic><topic>Hemoglobins - chemistry</topic><topic>Hemoglobins - metabolism</topic><topic>Hemolysis</topic><topic>Hep G2 Cells</topic><topic>Humans</topic><topic>Mice</topic><topic>Muramidase - chemistry</topic><topic>Muramidase - metabolism</topic><topic>Organometallic Compounds - chemical synthesis</topic><topic>Organometallic Compounds - chemistry</topic><topic>Organometallic Compounds - toxicity</topic><topic>Prodrugs - chemical synthesis</topic><topic>Prodrugs - chemistry</topic><topic>Prodrugs - toxicity</topic><topic>Protein Structure, Tertiary</topic><topic>Serum Albumin - chemistry</topic><topic>Serum Albumin - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Seixas, João D</creatorcontrib><creatorcontrib>Mukhopadhyay, Abhik</creatorcontrib><creatorcontrib>Santos-Silva, Teresa</creatorcontrib><creatorcontrib>Otterbein, Leo E</creatorcontrib><creatorcontrib>Gallo, David J</creatorcontrib><creatorcontrib>Rodrigues, Sandra S</creatorcontrib><creatorcontrib>Guerreiro, Bruno H</creatorcontrib><creatorcontrib>Gonçalves, Ana M L</creatorcontrib><creatorcontrib>Penacho, Nuno</creatorcontrib><creatorcontrib>Marques, Ana R</creatorcontrib><creatorcontrib>Coelho, Ana C</creatorcontrib><creatorcontrib>Reis, Patrícia M</creatorcontrib><creatorcontrib>Romão, Maria J</creatorcontrib><creatorcontrib>Romão, Carlos C</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Dalton transactions : an international journal of inorganic chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Seixas, João D</au><au>Mukhopadhyay, Abhik</au><au>Santos-Silva, Teresa</au><au>Otterbein, Leo E</au><au>Gallo, David J</au><au>Rodrigues, Sandra S</au><au>Guerreiro, Bruno H</au><au>Gonçalves, Ana M L</au><au>Penacho, Nuno</au><au>Marques, Ana R</au><au>Coelho, Ana C</au><au>Reis, Patrícia M</au><au>Romão, Maria J</au><au>Romão, Carlos C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characterization of a versatile organometallic pro-drug (CORM) for experimental CO based therapeutics</atitle><jtitle>Dalton transactions : an international journal of inorganic chemistry</jtitle><addtitle>Dalton Trans</addtitle><date>2013-05-07</date><risdate>2013</risdate><volume>42</volume><issue>17</issue><spage>5985</spage><epage>5998</epage><pages>5985-5998</pages><issn>1477-9226</issn><eissn>1477-9234</eissn><abstract>The complex fac-[Mo(CO)(3)(histidinate)]Na has been reported to be an effective CO-Releasing Molecule in vivo, eliciting therapeutic effects in several animal models of disease. The CO releasing profile of this complex in different settings both in vitro and in vivo reveals that the compound can readily liberate all of its three CO equivalents under biological conditions. The compound has low toxicity and cytotoxicity and is not hemolytic. CO release is accompanied by a decrease in arterial blood pressure following administration in vivo. We studied its behavior in solution and upon the interaction with proteins. Reactive oxygen species (ROS) generation upon exposure to air and polyoxomolybdate formation in soaks with lysozyme crystals were observed as processes ensuing from the decomposition of the complex and the release of CO.</abstract><cop>England</cop><pmid>23223860</pmid><doi>10.1039/c2dt32174b</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Royal Society Of Chemistry Journals 2008-; Alma/SFX Local Collection |
| subjects | Animals Binding Sites Carbon Monoxide - metabolism Cell Line Cell Survival - drug effects Coordination Complexes - chemical synthesis Coordination Complexes - chemistry Coordination Complexes - toxicity Crystallography, X-Ray Hemodynamics Hemoglobins - chemistry Hemoglobins - metabolism Hemolysis Hep G2 Cells Humans Mice Muramidase - chemistry Muramidase - metabolism Organometallic Compounds - chemical synthesis Organometallic Compounds - chemistry Organometallic Compounds - toxicity Prodrugs - chemical synthesis Prodrugs - chemistry Prodrugs - toxicity Protein Structure, Tertiary Serum Albumin - chemistry Serum Albumin - metabolism |
| title | Characterization of a versatile organometallic pro-drug (CORM) for experimental CO based therapeutics |
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