Squalenoyl Gemcitabine Monophosphate: Synthesis, Characterisation of Nanoassemblies and Biological Evaluation
Trialkylammonium 4‐(N)‐1,1′,2‐trisnor‐squalenoylgemcitabine monophosphate (SQdFdC‐MP) salts were prepared from 1,1′,2‐trisnor‐squalenoylgemcitabine by phosphoramidite‐type chemistry. This amphiphilic molecule self‐assembled into nanoassemblies of about 100 nm in size in aqueous solutions. Cryo‐TEM a...
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| Veröffentlicht in: | European Journal of Organic Chemistry 2011-05, Vol.2011 (14), p.2615-2628 |
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| container_title | European Journal of Organic Chemistry |
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| creator | Caron, Joachim Lepeltier, Elise Reddy, L. Harivardhan Lepêtre-Mouelhi, Sinda Wack, Séverine Bourgaux, Claudie Couvreur, Patrick Desmaële, Didier |
| description | Trialkylammonium 4‐(N)‐1,1′,2‐trisnor‐squalenoylgemcitabine monophosphate (SQdFdC‐MP) salts were prepared from 1,1′,2‐trisnor‐squalenoylgemcitabine by phosphoramidite‐type chemistry. This amphiphilic molecule self‐assembled into nanoassemblies of about 100 nm in size in aqueous solutions. Cryo‐TEM and small‐angle X‐ray scattering (SAXS) investigations revealed that SQdFdC‐MP molecules self‐organized into unilamellar liposomes with a membrane thickness of about 70 Å. Such liposomal trialkylammonium SQdFdC‐MP formulations displayed significant anticancer activity on leukaemia cells. These results suggested that squalene conjugates of negatively charged nucleotide analogues efficiently penetrated into tumour cells. Furthermore, triethylammonium SQdFdC‐MP nanoassemblies were found to be more active than the parent nucleoside towards the L1210 10 K resistant cell line.
Triethylammonium squalenoyl‐gemcitabine monophosphate self‐assembles into unilamellar liposomes of about one hundred nanometres in size. These nanoassemblies displayed a pronounced anticancer effect on leukaemia cell lines including a gemcitabine‐resistant cell line with down‐regulation of deoxycytidine kinase enzyme. |
| doi_str_mv | 10.1002/ejoc.201100036 |
| format | Article |
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Triethylammonium squalenoyl‐gemcitabine monophosphate self‐assembles into unilamellar liposomes of about one hundred nanometres in size. These nanoassemblies displayed a pronounced anticancer effect on leukaemia cell lines including a gemcitabine‐resistant cell line with down‐regulation of deoxycytidine kinase enzyme.</description><identifier>ISSN: 1434-193X</identifier><identifier>EISSN: 1099-0690</identifier><identifier>DOI: 10.1002/ejoc.201100036</identifier><language>eng</language><publisher>Weinheim: WILEY-VCH Verlag</publisher><subject>Antineoplastic agents ; Antitumor agents ; Biological and medical sciences ; Carbohydrates. Nucleosides and nucleotides ; Chemistry ; Cross-disciplinary physics: materials science; rheology ; Exact sciences and technology ; General aspects ; Materials science ; Medical sciences ; Medicinal chemistry ; Methods of nanofabrication ; Nanostructures ; Nucleosides ; Nucleosides, nucleotides and oligonucleotides ; Nucleotides ; Organic chemistry ; Pharmacology. Drug treatments ; Physics ; Preparations and properties ; Prodrugs ; Supramolecular and biochemical assembly</subject><ispartof>European Journal of Organic Chemistry, 2011-05, Vol.2011 (14), p.2615-2628</ispartof><rights>Copyright © 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3576-7059d6032bc0c122a21fc74db73165998bf87fd222cc68877c785032355f42cb3</citedby><cites>FETCH-LOGICAL-c3576-7059d6032bc0c122a21fc74db73165998bf87fd222cc68877c785032355f42cb3</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%2Fejoc.201100036$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fejoc.201100036$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>313,314,776,780,788,1411,27899,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24122770$$DView record in Pascal Francis$$Hfree_for_read</backlink></links><search><creatorcontrib>Caron, Joachim</creatorcontrib><creatorcontrib>Lepeltier, Elise</creatorcontrib><creatorcontrib>Reddy, L. Harivardhan</creatorcontrib><creatorcontrib>Lepêtre-Mouelhi, Sinda</creatorcontrib><creatorcontrib>Wack, Séverine</creatorcontrib><creatorcontrib>Bourgaux, Claudie</creatorcontrib><creatorcontrib>Couvreur, Patrick</creatorcontrib><creatorcontrib>Desmaële, Didier</creatorcontrib><title>Squalenoyl Gemcitabine Monophosphate: Synthesis, Characterisation of Nanoassemblies and Biological Evaluation</title><title>European Journal of Organic Chemistry</title><addtitle>Eur. J. Org. Chem</addtitle><description>Trialkylammonium 4‐(N)‐1,1′,2‐trisnor‐squalenoylgemcitabine monophosphate (SQdFdC‐MP) salts were prepared from 1,1′,2‐trisnor‐squalenoylgemcitabine by phosphoramidite‐type chemistry. This amphiphilic molecule self‐assembled into nanoassemblies of about 100 nm in size in aqueous solutions. Cryo‐TEM and small‐angle X‐ray scattering (SAXS) investigations revealed that SQdFdC‐MP molecules self‐organized into unilamellar liposomes with a membrane thickness of about 70 Å. Such liposomal trialkylammonium SQdFdC‐MP formulations displayed significant anticancer activity on leukaemia cells. These results suggested that squalene conjugates of negatively charged nucleotide analogues efficiently penetrated into tumour cells. Furthermore, triethylammonium SQdFdC‐MP nanoassemblies were found to be more active than the parent nucleoside towards the L1210 10 K resistant cell line.
Triethylammonium squalenoyl‐gemcitabine monophosphate self‐assembles into unilamellar liposomes of about one hundred nanometres in size. These nanoassemblies displayed a pronounced anticancer effect on leukaemia cell lines including a gemcitabine‐resistant cell line with down‐regulation of deoxycytidine kinase enzyme.</description><subject>Antineoplastic agents</subject><subject>Antitumor agents</subject><subject>Biological and medical sciences</subject><subject>Carbohydrates. Nucleosides and nucleotides</subject><subject>Chemistry</subject><subject>Cross-disciplinary physics: materials science; rheology</subject><subject>Exact sciences and technology</subject><subject>General aspects</subject><subject>Materials science</subject><subject>Medical sciences</subject><subject>Medicinal chemistry</subject><subject>Methods of nanofabrication</subject><subject>Nanostructures</subject><subject>Nucleosides</subject><subject>Nucleosides, nucleotides and oligonucleotides</subject><subject>Nucleotides</subject><subject>Organic chemistry</subject><subject>Pharmacology. Drug treatments</subject><subject>Physics</subject><subject>Preparations and properties</subject><subject>Prodrugs</subject><subject>Supramolecular and biochemical assembly</subject><issn>1434-193X</issn><issn>1099-0690</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><recordid>eNqFkD1PwzAQhiMEEqWwMnthI8UfiR2zQekHqLRDQXSzLq5DXdK4xCmQf09KUcXGdHfS89yd3iA4J7hDMKZXZul0h2LSDJjxg6BFsJQh5hIfNn3EopBINjsOTrxfNojknLSC1fR9A7kpXJ2jgVlpW0FqC4MeXeHWC-fXC6jMNZrWRbUw3vpL1F1ACboypfVQWVcgl6ExFA68N6s0t8YjKObo1rrcvVoNOep9QL75YU-Dowxyb85-azt47veeusNwNBncd29GoWax4KHAsZxzzGiqsSaUAiWZFtE8FYzwWMokzRKRzSmlWvMkEUKLJG5wFsdZRHXK2kFnt1eXzvvSZGpd2hWUtSJYbcNS27DUPqxGuNgJa_DNy1kJhbZ-b9Go-UII3HByx33a3NT_bFW9h0n3741w51pfma-9C-Wb4oKJWL2MB4rfDePRrN9XEfsG3eWLlg</recordid><startdate>201105</startdate><enddate>201105</enddate><creator>Caron, Joachim</creator><creator>Lepeltier, Elise</creator><creator>Reddy, L. Harivardhan</creator><creator>Lepêtre-Mouelhi, Sinda</creator><creator>Wack, Séverine</creator><creator>Bourgaux, Claudie</creator><creator>Couvreur, Patrick</creator><creator>Desmaële, Didier</creator><general>WILEY-VCH Verlag</general><general>WILEY‐VCH Verlag</general><general>Wiley-VCH</general><scope>BSCLL</scope><scope>IQODW</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>201105</creationdate><title>Squalenoyl Gemcitabine Monophosphate: Synthesis, Characterisation of Nanoassemblies and Biological Evaluation</title><author>Caron, Joachim ; Lepeltier, Elise ; Reddy, L. Harivardhan ; Lepêtre-Mouelhi, Sinda ; Wack, Séverine ; Bourgaux, Claudie ; Couvreur, Patrick ; Desmaële, Didier</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3576-7059d6032bc0c122a21fc74db73165998bf87fd222cc68877c785032355f42cb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Antineoplastic agents</topic><topic>Antitumor agents</topic><topic>Biological and medical sciences</topic><topic>Carbohydrates. Nucleosides and nucleotides</topic><topic>Chemistry</topic><topic>Cross-disciplinary physics: materials science; rheology</topic><topic>Exact sciences and technology</topic><topic>General aspects</topic><topic>Materials science</topic><topic>Medical sciences</topic><topic>Medicinal chemistry</topic><topic>Methods of nanofabrication</topic><topic>Nanostructures</topic><topic>Nucleosides</topic><topic>Nucleosides, nucleotides and oligonucleotides</topic><topic>Nucleotides</topic><topic>Organic chemistry</topic><topic>Pharmacology. Drug treatments</topic><topic>Physics</topic><topic>Preparations and properties</topic><topic>Prodrugs</topic><topic>Supramolecular and biochemical assembly</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Caron, Joachim</creatorcontrib><creatorcontrib>Lepeltier, Elise</creatorcontrib><creatorcontrib>Reddy, L. Harivardhan</creatorcontrib><creatorcontrib>Lepêtre-Mouelhi, Sinda</creatorcontrib><creatorcontrib>Wack, Séverine</creatorcontrib><creatorcontrib>Bourgaux, Claudie</creatorcontrib><creatorcontrib>Couvreur, Patrick</creatorcontrib><creatorcontrib>Desmaële, Didier</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>CrossRef</collection><jtitle>European Journal of Organic Chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Caron, Joachim</au><au>Lepeltier, Elise</au><au>Reddy, L. Harivardhan</au><au>Lepêtre-Mouelhi, Sinda</au><au>Wack, Séverine</au><au>Bourgaux, Claudie</au><au>Couvreur, Patrick</au><au>Desmaële, Didier</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Squalenoyl Gemcitabine Monophosphate: Synthesis, Characterisation of Nanoassemblies and Biological Evaluation</atitle><jtitle>European Journal of Organic Chemistry</jtitle><addtitle>Eur. J. Org. Chem</addtitle><date>2011-05</date><risdate>2011</risdate><volume>2011</volume><issue>14</issue><spage>2615</spage><epage>2628</epage><pages>2615-2628</pages><issn>1434-193X</issn><eissn>1099-0690</eissn><abstract>Trialkylammonium 4‐(N)‐1,1′,2‐trisnor‐squalenoylgemcitabine monophosphate (SQdFdC‐MP) salts were prepared from 1,1′,2‐trisnor‐squalenoylgemcitabine by phosphoramidite‐type chemistry. This amphiphilic molecule self‐assembled into nanoassemblies of about 100 nm in size in aqueous solutions. Cryo‐TEM and small‐angle X‐ray scattering (SAXS) investigations revealed that SQdFdC‐MP molecules self‐organized into unilamellar liposomes with a membrane thickness of about 70 Å. Such liposomal trialkylammonium SQdFdC‐MP formulations displayed significant anticancer activity on leukaemia cells. These results suggested that squalene conjugates of negatively charged nucleotide analogues efficiently penetrated into tumour cells. Furthermore, triethylammonium SQdFdC‐MP nanoassemblies were found to be more active than the parent nucleoside towards the L1210 10 K resistant cell line.
Triethylammonium squalenoyl‐gemcitabine monophosphate self‐assembles into unilamellar liposomes of about one hundred nanometres in size. These nanoassemblies displayed a pronounced anticancer effect on leukaemia cell lines including a gemcitabine‐resistant cell line with down‐regulation of deoxycytidine kinase enzyme.</abstract><cop>Weinheim</cop><pub>WILEY-VCH Verlag</pub><doi>10.1002/ejoc.201100036</doi><tpages>14</tpages></addata></record> |
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| subjects | Antineoplastic agents Antitumor agents Biological and medical sciences Carbohydrates. Nucleosides and nucleotides Chemistry Cross-disciplinary physics: materials science rheology Exact sciences and technology General aspects Materials science Medical sciences Medicinal chemistry Methods of nanofabrication Nanostructures Nucleosides Nucleosides, nucleotides and oligonucleotides Nucleotides Organic chemistry Pharmacology. Drug treatments Physics Preparations and properties Prodrugs Supramolecular and biochemical assembly |
| title | Squalenoyl Gemcitabine Monophosphate: Synthesis, Characterisation of Nanoassemblies and Biological Evaluation |
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