Pyridinium Cationic Lipids in Gene Delivery: A Structure−Activity Correlation Study
Three series of pyridinium cationic lipids useful as nonviral gene delivery agents were prepared by reaction of pyrylium salts with aminodiols, followed by acylation with fatty acyl chlorides. On the basis of this set of compounds, we undertook a comprehensive structure−activity relationship study a...
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| Veröffentlicht in: | Journal of medicinal chemistry 2004-07, Vol.47 (15), p.3744-3754 |
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| container_title | Journal of medicinal chemistry |
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| creator | Ilies, Marc Antoniu Seitz, William A Ghiviriga, Ion Johnson, Betty H Miller, Aaron Thompson, E. Brad Balaban, Alexandru T |
| description | Three series of pyridinium cationic lipids useful as nonviral gene delivery agents were prepared by reaction of pyrylium salts with aminodiols, followed by acylation with fatty acyl chlorides. On the basis of this set of compounds, we undertook a comprehensive structure−activity relationship study at the level of the linker, hydrophobic anchor, and counterion in order to identify the structural elements that generate the highest transfection efficiency for this new type of cationic lipid. The results revealed that when formulated with cholesterol at a 1:1 molar ratio, the 1-(1,3-dimyristoyloxyprop-2-yl)-2,4,6-trimethylpyridinium, under the form of hexafluorophosphate (5AMyr) or chloride (5DMyr), was able to transfect NCI-H23 lung carcinoma with efficiencies surpassing classic DOTAP-based formulations and with lower cytotoxicity. Subsequent tests on other malignancies yielded similarly promising results. |
| doi_str_mv | 10.1021/jm0499763 |
| format | Article |
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Brad ; Balaban, Alexandru T</creator><creatorcontrib>Ilies, Marc Antoniu ; Seitz, William A ; Ghiviriga, Ion ; Johnson, Betty H ; Miller, Aaron ; Thompson, E. Brad ; Balaban, Alexandru T</creatorcontrib><description>Three series of pyridinium cationic lipids useful as nonviral gene delivery agents were prepared by reaction of pyrylium salts with aminodiols, followed by acylation with fatty acyl chlorides. On the basis of this set of compounds, we undertook a comprehensive structure−activity relationship study at the level of the linker, hydrophobic anchor, and counterion in order to identify the structural elements that generate the highest transfection efficiency for this new type of cationic lipid. The results revealed that when formulated with cholesterol at a 1:1 molar ratio, the 1-(1,3-dimyristoyloxyprop-2-yl)-2,4,6-trimethylpyridinium, under the form of hexafluorophosphate (5AMyr) or chloride (5DMyr), was able to transfect NCI-H23 lung carcinoma with efficiencies surpassing classic DOTAP-based formulations and with lower cytotoxicity. Subsequent tests on other malignancies yielded similarly promising results.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm0499763</identifier><identifier>PMID: 15239653</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Biological and medical sciences ; Biotechnology ; Cations ; Cell Line, Tumor ; Cell Survival - drug effects ; Cholesterol - chemistry ; Diglycerides - chemical synthesis ; Diglycerides - chemistry ; Diglycerides - toxicity ; DNA - administration & dosage ; DNA - chemistry ; Drug Carriers - chemical synthesis ; Drug Carriers - chemistry ; Drug Carriers - toxicity ; Fundamental and applied biological sciences. Psychology ; Gene therapy ; Gene Transfer Techniques ; Health. Pharmaceutical industry ; Humans ; Industrial applications and implications. Economical aspects ; Lipids - chemical synthesis ; Lipids - chemistry ; Liposomes ; Molecular Structure ; Pyridinium Compounds - chemical synthesis ; Pyridinium Compounds - chemistry ; Pyridinium Compounds - toxicity ; Structure-Activity Relationship ; Transfection ; Ultrasonics</subject><ispartof>Journal of medicinal chemistry, 2004-07, Vol.47 (15), p.3744-3754</ispartof><rights>Copyright © 2004 American Chemical Society</rights><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a379t-2f48368875e7ceb1ba3b200e39c73556e4ee7a7800e241f21ae9d9d2fb944c753</citedby><cites>FETCH-LOGICAL-a379t-2f48368875e7ceb1ba3b200e39c73556e4ee7a7800e241f21ae9d9d2fb944c753</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/jm0499763$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm0499763$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15940084$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15239653$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ilies, Marc Antoniu</creatorcontrib><creatorcontrib>Seitz, William A</creatorcontrib><creatorcontrib>Ghiviriga, Ion</creatorcontrib><creatorcontrib>Johnson, Betty H</creatorcontrib><creatorcontrib>Miller, Aaron</creatorcontrib><creatorcontrib>Thompson, E. Brad</creatorcontrib><creatorcontrib>Balaban, Alexandru T</creatorcontrib><title>Pyridinium Cationic Lipids in Gene Delivery: A Structure−Activity Correlation Study</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>Three series of pyridinium cationic lipids useful as nonviral gene delivery agents were prepared by reaction of pyrylium salts with aminodiols, followed by acylation with fatty acyl chlorides. On the basis of this set of compounds, we undertook a comprehensive structure−activity relationship study at the level of the linker, hydrophobic anchor, and counterion in order to identify the structural elements that generate the highest transfection efficiency for this new type of cationic lipid. The results revealed that when formulated with cholesterol at a 1:1 molar ratio, the 1-(1,3-dimyristoyloxyprop-2-yl)-2,4,6-trimethylpyridinium, under the form of hexafluorophosphate (5AMyr) or chloride (5DMyr), was able to transfect NCI-H23 lung carcinoma with efficiencies surpassing classic DOTAP-based formulations and with lower cytotoxicity. Subsequent tests on other malignancies yielded similarly promising results.</description><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>Cations</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - drug effects</subject><subject>Cholesterol - chemistry</subject><subject>Diglycerides - chemical synthesis</subject><subject>Diglycerides - chemistry</subject><subject>Diglycerides - toxicity</subject><subject>DNA - administration & dosage</subject><subject>DNA - chemistry</subject><subject>Drug Carriers - chemical synthesis</subject><subject>Drug Carriers - chemistry</subject><subject>Drug Carriers - toxicity</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene therapy</subject><subject>Gene Transfer Techniques</subject><subject>Health. Pharmaceutical industry</subject><subject>Humans</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Lipids - chemical synthesis</subject><subject>Lipids - chemistry</subject><subject>Liposomes</subject><subject>Molecular Structure</subject><subject>Pyridinium Compounds - chemical synthesis</subject><subject>Pyridinium Compounds - chemistry</subject><subject>Pyridinium Compounds - toxicity</subject><subject>Structure-Activity Relationship</subject><subject>Transfection</subject><subject>Ultrasonics</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>eNpt0MtKw0AUBuBBFK3VhS8g2bhwEZ1bMhl3td4pWGgVcTNMJicwtU3LTCJm51K3PmKfxGhL68LVgXM-fg4_QgcEnxBMyelogrmUImYbqEUiikOeYL6JWhhTGtKYsh206_0IY8wIZdtop0FMxhFroad-7WxmC1tNgq4u7bSwJujZmc18YIvgGgoILmBsX8HVZ_P3z6ATDEpXmbJyMP_46pjSvtqyDrpT52D8G9CAKqv30Fauxx72l7ONHq4uh92bsHd_fdvt9ELNhCxDmvOExUkiIhAGUpJqllKMgUkjWBTFwAGEFkmzopzklGiQmcxonkrOjYhYGx0vco2beu8gVzNnJ9rVimD1045atdPYw4WdVekEsrVc1tGAoyXQ3uhx7nRhrP_jJMc44Y0LF876Et5Wd-1eVCyYiNSwP1DkmZ0nvbtHNVznauPVaFq5oqnknwe_AURDiPs</recordid><startdate>20040715</startdate><enddate>20040715</enddate><creator>Ilies, Marc Antoniu</creator><creator>Seitz, William A</creator><creator>Ghiviriga, Ion</creator><creator>Johnson, Betty H</creator><creator>Miller, Aaron</creator><creator>Thompson, E. Brad</creator><creator>Balaban, Alexandru T</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></search><sort><creationdate>20040715</creationdate><title>Pyridinium Cationic Lipids in Gene Delivery: A Structure−Activity Correlation Study</title><author>Ilies, Marc Antoniu ; Seitz, William A ; Ghiviriga, Ion ; Johnson, Betty H ; Miller, Aaron ; Thompson, E. Brad ; Balaban, Alexandru T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a379t-2f48368875e7ceb1ba3b200e39c73556e4ee7a7800e241f21ae9d9d2fb944c753</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Biological and medical sciences</topic><topic>Biotechnology</topic><topic>Cations</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival - drug effects</topic><topic>Cholesterol - chemistry</topic><topic>Diglycerides - chemical synthesis</topic><topic>Diglycerides - chemistry</topic><topic>Diglycerides - toxicity</topic><topic>DNA - administration & dosage</topic><topic>DNA - chemistry</topic><topic>Drug Carriers - chemical synthesis</topic><topic>Drug Carriers - chemistry</topic><topic>Drug Carriers - toxicity</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene therapy</topic><topic>Gene Transfer Techniques</topic><topic>Health. Pharmaceutical industry</topic><topic>Humans</topic><topic>Industrial applications and implications. Economical aspects</topic><topic>Lipids - chemical synthesis</topic><topic>Lipids - chemistry</topic><topic>Liposomes</topic><topic>Molecular Structure</topic><topic>Pyridinium Compounds - chemical synthesis</topic><topic>Pyridinium Compounds - chemistry</topic><topic>Pyridinium Compounds - toxicity</topic><topic>Structure-Activity Relationship</topic><topic>Transfection</topic><topic>Ultrasonics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ilies, Marc Antoniu</creatorcontrib><creatorcontrib>Seitz, William A</creatorcontrib><creatorcontrib>Ghiviriga, Ion</creatorcontrib><creatorcontrib>Johnson, Betty H</creatorcontrib><creatorcontrib>Miller, Aaron</creatorcontrib><creatorcontrib>Thompson, E. Brad</creatorcontrib><creatorcontrib>Balaban, Alexandru T</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><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ilies, Marc Antoniu</au><au>Seitz, William A</au><au>Ghiviriga, Ion</au><au>Johnson, Betty H</au><au>Miller, Aaron</au><au>Thompson, E. Brad</au><au>Balaban, Alexandru T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pyridinium Cationic Lipids in Gene Delivery: A Structure−Activity Correlation Study</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>2004-07-15</date><risdate>2004</risdate><volume>47</volume><issue>15</issue><spage>3744</spage><epage>3754</epage><pages>3744-3754</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>Three series of pyridinium cationic lipids useful as nonviral gene delivery agents were prepared by reaction of pyrylium salts with aminodiols, followed by acylation with fatty acyl chlorides. On the basis of this set of compounds, we undertook a comprehensive structure−activity relationship study at the level of the linker, hydrophobic anchor, and counterion in order to identify the structural elements that generate the highest transfection efficiency for this new type of cationic lipid. The results revealed that when formulated with cholesterol at a 1:1 molar ratio, the 1-(1,3-dimyristoyloxyprop-2-yl)-2,4,6-trimethylpyridinium, under the form of hexafluorophosphate (5AMyr) or chloride (5DMyr), was able to transfect NCI-H23 lung carcinoma with efficiencies surpassing classic DOTAP-based formulations and with lower cytotoxicity. Subsequent tests on other malignancies yielded similarly promising results.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>15239653</pmid><doi>10.1021/jm0499763</doi><tpages>11</tpages></addata></record> |
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| source | MEDLINE; American Chemical Society Journals |
| subjects | Biological and medical sciences Biotechnology Cations Cell Line, Tumor Cell Survival - drug effects Cholesterol - chemistry Diglycerides - chemical synthesis Diglycerides - chemistry Diglycerides - toxicity DNA - administration & dosage DNA - chemistry Drug Carriers - chemical synthesis Drug Carriers - chemistry Drug Carriers - toxicity Fundamental and applied biological sciences. Psychology Gene therapy Gene Transfer Techniques Health. Pharmaceutical industry Humans Industrial applications and implications. Economical aspects Lipids - chemical synthesis Lipids - chemistry Liposomes Molecular Structure Pyridinium Compounds - chemical synthesis Pyridinium Compounds - chemistry Pyridinium Compounds - toxicity Structure-Activity Relationship Transfection Ultrasonics |
| title | Pyridinium Cationic Lipids in Gene Delivery: A Structure−Activity Correlation Study |
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