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Synthesis of Antimitotic Thioglycosides: In Vitro and in Vivo Evaluation of Their Anticancer Activity
The synthesis and biological activity of oleylN-acetyl-α- and β-d-glucosaminides (1 and 2, respectively) and their thioglycosyl analogues (3 and 4, respectively) are reported. The compounds exhibited antimitotic activity on rat glioma (C6) and human lung carcinoma (A549) cell cultures in the micromo...
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| Published in: | Journal of medicinal chemistry 2011-10, Vol.54 (19), p.6949-6955 |
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| Main Authors: | , , , , , , , |
| Format: | Article |
| Language: | English |
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| cited_by | cdi_FETCH-LOGICAL-a383t-f0ae8786e24d673229544ac745071a8f54cbc9c72bec1032c70b844db7f67ba73 |
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| cites | cdi_FETCH-LOGICAL-a383t-f0ae8786e24d673229544ac745071a8f54cbc9c72bec1032c70b844db7f67ba73 |
| container_end_page | 6955 |
| container_issue | 19 |
| container_start_page | 6949 |
| container_title | Journal of medicinal chemistry |
| container_volume | 54 |
| creator | García-Álvarez, Isabel Groult, Hugo Casas, Josefina Barreda-Manso, M. Asunción Yanguas-Casás, Natalia Nieto-Sampedro, Manuel Romero-Ramírez, Lorenzo Fernández-Mayoralas, Alfonso |
| description | The synthesis and biological activity of oleylN-acetyl-α- and β-d-glucosaminides (1 and 2, respectively) and their thioglycosyl analogues (3 and 4, respectively) are reported. The compounds exhibited antimitotic activity on rat glioma (C6) and human lung carcinoma (A549) cell cultures in the micromolar range. Analysis of cell extracts using ultra performance liquid chromatography–mass spectrometry showed that the synthetic glycosides produce alterations in glycosphingolipid metabolism, with variable effect on the level of glucosylceramide depending on the configuration of the antimitotic used. In vivo experiments in nude mice bearing an implanted C6 glioma showed that the α-thioglycoside 3 reduced tumor volume, while the O-glycosyl derivative was inactive, highlighting the importance of using enzyme resistant glycosides. |
| doi_str_mv | 10.1021/jm200961q |
| format | article |
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In vivo experiments in nude mice bearing an implanted C6 glioma showed that the α-thioglycoside 3 reduced tumor volume, while the O-glycosyl derivative was inactive, highlighting the importance of using enzyme resistant glycosides.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm200961q</identifier><identifier>PMID: 21866909</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Animals ; Antimitotic Agents - chemical synthesis ; Antimitotic Agents - chemistry ; Antimitotic Agents - pharmacology ; beta-N-Acetylhexosaminidases - chemistry ; Cancer ; Cell Line, Tumor ; Chemical Sciences ; Drug Screening Assays, Antitumor ; Glycolipids - chemical synthesis ; Glycolipids - chemistry ; Glycolipids - pharmacology ; Humans ; Hydrolysis ; Life Sciences ; Medicinal Chemistry ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Organic chemistry ; Rats ; Structure-Activity Relationship ; Thioglucosides - chemical synthesis ; Thioglucosides - chemistry ; Thioglucosides - pharmacology ; Thioglycosides - chemical synthesis ; Thioglycosides - chemistry ; Thioglycosides - pharmacology ; Transplantation, Heterologous ; Tumor Burden - drug effects</subject><ispartof>Journal of medicinal chemistry, 2011-10, Vol.54 (19), p.6949-6955</ispartof><rights>Copyright © 2011 American Chemical Society</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a383t-f0ae8786e24d673229544ac745071a8f54cbc9c72bec1032c70b844db7f67ba73</citedby><cites>FETCH-LOGICAL-a383t-f0ae8786e24d673229544ac745071a8f54cbc9c72bec1032c70b844db7f67ba73</cites><orcidid>0000-0002-1571-9400</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21866909$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://univ-rochelle.hal.science/hal-01943907$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>García-Álvarez, Isabel</creatorcontrib><creatorcontrib>Groult, Hugo</creatorcontrib><creatorcontrib>Casas, Josefina</creatorcontrib><creatorcontrib>Barreda-Manso, M. Asunción</creatorcontrib><creatorcontrib>Yanguas-Casás, Natalia</creatorcontrib><creatorcontrib>Nieto-Sampedro, Manuel</creatorcontrib><creatorcontrib>Romero-Ramírez, Lorenzo</creatorcontrib><creatorcontrib>Fernández-Mayoralas, Alfonso</creatorcontrib><title>Synthesis of Antimitotic Thioglycosides: In Vitro and in Vivo Evaluation of Their Anticancer Activity</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>The synthesis and biological activity of oleylN-acetyl-α- and β-d-glucosaminides (1 and 2, respectively) and their thioglycosyl analogues (3 and 4, respectively) are reported. The compounds exhibited antimitotic activity on rat glioma (C6) and human lung carcinoma (A549) cell cultures in the micromolar range. Analysis of cell extracts using ultra performance liquid chromatography–mass spectrometry showed that the synthetic glycosides produce alterations in glycosphingolipid metabolism, with variable effect on the level of glucosylceramide depending on the configuration of the antimitotic used. In vivo experiments in nude mice bearing an implanted C6 glioma showed that the α-thioglycoside 3 reduced tumor volume, while the O-glycosyl derivative was inactive, highlighting the importance of using enzyme resistant glycosides.</description><subject>Animals</subject><subject>Antimitotic Agents - chemical synthesis</subject><subject>Antimitotic Agents - chemistry</subject><subject>Antimitotic Agents - pharmacology</subject><subject>beta-N-Acetylhexosaminidases - chemistry</subject><subject>Cancer</subject><subject>Cell Line, Tumor</subject><subject>Chemical Sciences</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Glycolipids - chemical synthesis</subject><subject>Glycolipids - chemistry</subject><subject>Glycolipids - pharmacology</subject><subject>Humans</subject><subject>Hydrolysis</subject><subject>Life Sciences</subject><subject>Medicinal Chemistry</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Neoplasm Transplantation</subject><subject>Organic chemistry</subject><subject>Rats</subject><subject>Structure-Activity Relationship</subject><subject>Thioglucosides - chemical synthesis</subject><subject>Thioglucosides - chemistry</subject><subject>Thioglucosides - pharmacology</subject><subject>Thioglycosides - chemical synthesis</subject><subject>Thioglycosides - chemistry</subject><subject>Thioglycosides - pharmacology</subject><subject>Transplantation, Heterologous</subject><subject>Tumor Burden - drug effects</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><recordid>eNptkbtOwzAUhi0EgnIZeAGUBSGGwPGlsc1WVUCRKjFQWC3HcairJG5jp1LfnpRCWZjORd_5hv8gdInhDgPB94uaAMgMrw7QAA8JpEwAO0QDAEJSkhF6gk5DWAAAxYQeoxOCRZZJkANk3zZNnNvgQuLLZNREV7voozPJbO78Z7UxPrjChofkpUk-XGx9opsicdth7ZPHta46HZ1vtuezuXXtt8Toxti-NdGtXdyco6NSV8Fe_NQz9P70OBtP0unr88t4NE01FTSmJWgruMgsYUXGKSFyyJg2nA2BYy3KITO5kYaT3BoMlBgOuWCsyHmZ8VxzeoZud965rtSydbVuN8prpyajqdruAEtGJfA17tmbHbts_aqzIaraBWOrSjfWd0EJmQkiJZZ_VtP6EFpb7tUY1PYBav-Anr36sXZ5bYs9-Zt4D1zvAG2CWviubfpA_hF9Aashi9E</recordid><startdate>20111013</startdate><enddate>20111013</enddate><creator>García-Álvarez, Isabel</creator><creator>Groult, Hugo</creator><creator>Casas, Josefina</creator><creator>Barreda-Manso, M. Asunción</creator><creator>Yanguas-Casás, Natalia</creator><creator>Nieto-Sampedro, Manuel</creator><creator>Romero-Ramírez, Lorenzo</creator><creator>Fernández-Mayoralas, Alfonso</creator><general>American Chemical Society</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><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-1571-9400</orcidid></search><sort><creationdate>20111013</creationdate><title>Synthesis of Antimitotic Thioglycosides: In Vitro and in Vivo Evaluation of Their Anticancer Activity</title><author>García-Álvarez, Isabel ; Groult, Hugo ; Casas, Josefina ; Barreda-Manso, M. 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Asunción</creatorcontrib><creatorcontrib>Yanguas-Casás, Natalia</creatorcontrib><creatorcontrib>Nieto-Sampedro, Manuel</creatorcontrib><creatorcontrib>Romero-Ramírez, Lorenzo</creatorcontrib><creatorcontrib>Fernández-Mayoralas, Alfonso</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><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>García-Álvarez, Isabel</au><au>Groult, Hugo</au><au>Casas, Josefina</au><au>Barreda-Manso, M. Asunción</au><au>Yanguas-Casás, Natalia</au><au>Nieto-Sampedro, Manuel</au><au>Romero-Ramírez, Lorenzo</au><au>Fernández-Mayoralas, Alfonso</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis of Antimitotic Thioglycosides: In Vitro and in Vivo Evaluation of Their Anticancer Activity</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>2011-10-13</date><risdate>2011</risdate><volume>54</volume><issue>19</issue><spage>6949</spage><epage>6955</epage><pages>6949-6955</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><abstract>The synthesis and biological activity of oleylN-acetyl-α- and β-d-glucosaminides (1 and 2, respectively) and their thioglycosyl analogues (3 and 4, respectively) are reported. The compounds exhibited antimitotic activity on rat glioma (C6) and human lung carcinoma (A549) cell cultures in the micromolar range. Analysis of cell extracts using ultra performance liquid chromatography–mass spectrometry showed that the synthetic glycosides produce alterations in glycosphingolipid metabolism, with variable effect on the level of glucosylceramide depending on the configuration of the antimitotic used. In vivo experiments in nude mice bearing an implanted C6 glioma showed that the α-thioglycoside 3 reduced tumor volume, while the O-glycosyl derivative was inactive, highlighting the importance of using enzyme resistant glycosides.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>21866909</pmid><doi>10.1021/jm200961q</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-1571-9400</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-2623 |
| ispartof | Journal of medicinal chemistry, 2011-10, Vol.54 (19), p.6949-6955 |
| issn | 0022-2623 1520-4804 |
| language | eng |
| recordid | cdi_hal_primary_oai_HAL_hal_01943907v1 |
| source | American Chemical Society:Jisc Collections:American Chemical Society Read & Publish Agreement 2022-2024 (Reading list) |
| subjects | Animals Antimitotic Agents - chemical synthesis Antimitotic Agents - chemistry Antimitotic Agents - pharmacology beta-N-Acetylhexosaminidases - chemistry Cancer Cell Line, Tumor Chemical Sciences Drug Screening Assays, Antitumor Glycolipids - chemical synthesis Glycolipids - chemistry Glycolipids - pharmacology Humans Hydrolysis Life Sciences Medicinal Chemistry Mice Mice, Nude Neoplasm Transplantation Organic chemistry Rats Structure-Activity Relationship Thioglucosides - chemical synthesis Thioglucosides - chemistry Thioglucosides - pharmacology Thioglycosides - chemical synthesis Thioglycosides - chemistry Thioglycosides - pharmacology Transplantation, Heterologous Tumor Burden - drug effects |
| title | Synthesis of Antimitotic Thioglycosides: In Vitro and in Vivo Evaluation of Their Anticancer Activity |
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