Synthesis and Antiviral Evaluation of 1-O-Hexadecylpropanediol-3-P-acyclovir: Efficacy Against HSV-1 Infection in Mice
We synthesized, 1-O-hexadecylpropanediol-3-P-acyclovir, an orally bioavailable lipid prodrug of acyclovir and evaluated it for in vitro and in vivo activity against herpes simplex virus infections. Although 1-O-hexadecylpropanediol-3-P-acyclovir was less active in vitro than acyclovir, on a molar ba...
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| Veröffentlicht in: | Nucleosides, nucleotides & nucleic acids nucleotides & nucleic acids, 2000-01, Vol.19 (1-2), p.471-479 |
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| container_end_page | 479 |
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| container_issue | 1-2 |
| container_start_page | 471 |
| container_title | Nucleosides, nucleotides & nucleic acids |
| container_volume | 19 |
| creator | Beadle, James R. Kini, Ganesh D. Aldern, Kathy A. Gardner, Michael F. Wright, Kristine N. Rybak, Rachel J. Kern, Earl R. Hostetler, Karl Y. |
| description | We synthesized, 1-O-hexadecylpropanediol-3-P-acyclovir, an orally bioavailable lipid prodrug of acyclovir and evaluated it for in vitro and in vivo activity against herpes simplex virus infections. Although 1-O-hexadecylpropanediol-3-P-acyclovir was less active in vitro than acyclovir, on a molar basis it was 2.4 times more active orally in preventing mortality from acute HSV-1 infection in mice. In vitro, 1-O-hexadecylpropanediol-3-P-acyclovir was also more active than acyclovir in a thymidine kinase negative mutant strain of HSV-1 (DM21) and had somewhat higher activity in cytomegalovirus infection in vitro due to it's ability to bypass thymidine kinase. |
| doi_str_mv | 10.1080/15257770008033022 |
| format | Article |
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Although 1-O-hexadecylpropanediol-3-P-acyclovir was less active in vitro than acyclovir, on a molar basis it was 2.4 times more active orally in preventing mortality from acute HSV-1 infection in mice. In vitro, 1-O-hexadecylpropanediol-3-P-acyclovir was also more active than acyclovir in a thymidine kinase negative mutant strain of HSV-1 (DM21) and had somewhat higher activity in cytomegalovirus infection in vitro due to it's ability to bypass thymidine kinase.</description><identifier>ISSN: 1525-7770</identifier><identifier>EISSN: 1532-2335</identifier><identifier>DOI: 10.1080/15257770008033022</identifier><identifier>PMID: 10772728</identifier><language>eng</language><publisher>United States: Taylor & Francis Group</publisher><subject>Acyclovir - administration & dosage ; Acyclovir - analogs & derivatives ; Acyclovir - chemical synthesis ; Acyclovir - pharmacology ; Administration, Oral ; Animals ; Antiviral Agents - administration & dosage ; Antiviral Agents - chemical synthesis ; Antiviral Agents - pharmacology ; Cytomegalovirus - drug effects ; Encephalitis, Herpes Simplex - drug therapy ; Female ; Herpesvirus 1, Human - drug effects ; Herpesvirus 1, Human - genetics ; Mice ; Mice, Inbred BALB C ; Mutation ; Prodrugs - administration & dosage ; Prodrugs - chemical synthesis ; Prodrugs - pharmacology ; Thymidine Kinase - genetics</subject><ispartof>Nucleosides, nucleotides & nucleic acids, 2000-01, Vol.19 (1-2), p.471-479</ispartof><rights>Copyright Taylor & Francis Group, LLC 2000</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c398t-d1fe02a8bbf6d220d5e03ab6b5ab19c269821c9ceca38cb35a7b25c17167743b3</citedby><cites>FETCH-LOGICAL-c398t-d1fe02a8bbf6d220d5e03ab6b5ab19c269821c9ceca38cb35a7b25c17167743b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.tandfonline.com/doi/pdf/10.1080/15257770008033022$$EPDF$$P50$$Ginformaworld$$H</linktopdf><linktohtml>$$Uhttps://www.tandfonline.com/doi/full/10.1080/15257770008033022$$EHTML$$P50$$Ginformaworld$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,59647,60436</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10772728$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Beadle, James R.</creatorcontrib><creatorcontrib>Kini, Ganesh D.</creatorcontrib><creatorcontrib>Aldern, Kathy A.</creatorcontrib><creatorcontrib>Gardner, Michael F.</creatorcontrib><creatorcontrib>Wright, Kristine N.</creatorcontrib><creatorcontrib>Rybak, Rachel J.</creatorcontrib><creatorcontrib>Kern, Earl R.</creatorcontrib><creatorcontrib>Hostetler, Karl Y.</creatorcontrib><title>Synthesis and Antiviral Evaluation of 1-O-Hexadecylpropanediol-3-P-acyclovir: Efficacy Against HSV-1 Infection in Mice</title><title>Nucleosides, nucleotides & nucleic acids</title><addtitle>Nucleosides Nucleotides Nucleic Acids</addtitle><description>We synthesized, 1-O-hexadecylpropanediol-3-P-acyclovir, an orally bioavailable lipid prodrug of acyclovir and evaluated it for in vitro and in vivo activity against herpes simplex virus infections. Although 1-O-hexadecylpropanediol-3-P-acyclovir was less active in vitro than acyclovir, on a molar basis it was 2.4 times more active orally in preventing mortality from acute HSV-1 infection in mice. In vitro, 1-O-hexadecylpropanediol-3-P-acyclovir was also more active than acyclovir in a thymidine kinase negative mutant strain of HSV-1 (DM21) and had somewhat higher activity in cytomegalovirus infection in vitro due to it's ability to bypass thymidine kinase.</description><subject>Acyclovir - administration & dosage</subject><subject>Acyclovir - analogs & derivatives</subject><subject>Acyclovir - chemical synthesis</subject><subject>Acyclovir - pharmacology</subject><subject>Administration, Oral</subject><subject>Animals</subject><subject>Antiviral Agents - administration & dosage</subject><subject>Antiviral Agents - chemical synthesis</subject><subject>Antiviral Agents - pharmacology</subject><subject>Cytomegalovirus - drug effects</subject><subject>Encephalitis, Herpes Simplex - drug therapy</subject><subject>Female</subject><subject>Herpesvirus 1, Human - drug effects</subject><subject>Herpesvirus 1, Human - genetics</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mutation</subject><subject>Prodrugs - administration & dosage</subject><subject>Prodrugs - chemical synthesis</subject><subject>Prodrugs - pharmacology</subject><subject>Thymidine Kinase - genetics</subject><issn>1525-7770</issn><issn>1532-2335</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1rVDEUhoMo9kN_gBvJyl1qTmImd8TNUEanUGmh6vZybm6ikUwyJplp779vxumiUMRVcuB5Xl5eQt4APwPe8feghNJac94OKbkQz8gxKCmYkFI93_-FYnvgiJyU8ptz6HinX5Ij4FoLLbpjsruZYv1liy8U40gXsfqdzxjocodhi9WnSJOjwK7Yyt7haM0UNjltMNrRp8Aku2ZoJhNS0z7SpXPetJsufqKPpdLVzQ8G9CI6a_5m-Ui_emNfkRcOQ7GvH95T8v3z8tv5il1efbk4X1wyI-ddZSM4ywV2w-BmoxB8VJZLHGaDwgHmRszmnQAzN9ag7MwgFepBKAMaZlp_kIM8Je8Oua3zn60ttV_7YmwIrX_all4DV6AUNBAOoMmplGxdv8l-jXnqgff7sfsnYzfn7UP4dljb8ZFxWLcB-gD46FJe423KYewrTiFllzEaX57G9vWuNvPTf03572b3pbufCw</recordid><startdate>20000101</startdate><enddate>20000101</enddate><creator>Beadle, James R.</creator><creator>Kini, Ganesh D.</creator><creator>Aldern, Kathy A.</creator><creator>Gardner, Michael F.</creator><creator>Wright, Kristine N.</creator><creator>Rybak, Rachel J.</creator><creator>Kern, Earl R.</creator><creator>Hostetler, Karl Y.</creator><general>Taylor & Francis Group</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></search><sort><creationdate>20000101</creationdate><title>Synthesis and Antiviral Evaluation of 1-O-Hexadecylpropanediol-3-P-acyclovir: Efficacy Against HSV-1 Infection in Mice</title><author>Beadle, James R. ; 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| subjects | Acyclovir - administration & dosage Acyclovir - analogs & derivatives Acyclovir - chemical synthesis Acyclovir - pharmacology Administration, Oral Animals Antiviral Agents - administration & dosage Antiviral Agents - chemical synthesis Antiviral Agents - pharmacology Cytomegalovirus - drug effects Encephalitis, Herpes Simplex - drug therapy Female Herpesvirus 1, Human - drug effects Herpesvirus 1, Human - genetics Mice Mice, Inbred BALB C Mutation Prodrugs - administration & dosage Prodrugs - chemical synthesis Prodrugs - pharmacology Thymidine Kinase - genetics |
| title | Synthesis and Antiviral Evaluation of 1-O-Hexadecylpropanediol-3-P-acyclovir: Efficacy Against HSV-1 Infection in Mice |
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