Syntheses and biological evaluations of 3'-deoxy-3'-C-branched-chain-substituted nucleosides
Various 3'-deoxy-3'-C-(hydroxymethyl)-, 3'-deoxy-3'-C-(fluoromethyl)-, 3'-deoxy-3'-C-(azidomethyl)-, and 3'-deoxy-3'-C-(aminomethyl)-substituted nucleosides (total 12 compounds) have been synthesized and evaluated against L1210, P388, S-180, and CCRF-CEM cells...
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| Veröffentlicht in: | Journal of medicinal chemistry 1993-02, Vol.36 (3), p.353-362 |
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| container_title | Journal of medicinal chemistry |
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| creator | Lin, Tai Shun Zhu, Ju Liang Dutschman, Ginger E Cheng, Yung Chi Prusoff, William H |
| description | Various 3'-deoxy-3'-C-(hydroxymethyl)-, 3'-deoxy-3'-C-(fluoromethyl)-, 3'-deoxy-3'-C-(azidomethyl)-, and 3'-deoxy-3'-C-(aminomethyl)-substituted nucleosides (total 12 compounds) have been synthesized and evaluated against L1210, P388, S-180, and CCRF-CEM cells and HSV-1, HSV-2, and HIV-1 in culture. Only 3'-deoxy-3'-C-(hydroxymethyl)thymidine (36) was found to show significant anticancer activity against L1210, P388, S-180, and CCRF-CEM cells with ED50 values of 50, 5, 10, and 1 microM, respectively. None of these compounds demonstrated significant antiviral activity against HSV-1, HSV-2, or HIV-1. These compounds were also evaluated against thymidine kinases derived from HSV-I (strain KOS), HSV-2 (strain 333), and mammalian (K562) cells. The thymidine kinase (HSV-1 strain KOS) was inhibited significantly by both 3'-deoxy-3'-C-(hydroxymethyl)- and 3'-deoxy-3'-C-(fluoromethyl)thymidine. |
| doi_str_mv | 10.1021/jm00055a006 |
| format | Article |
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Only 3'-deoxy-3'-C-(hydroxymethyl)thymidine (36) was found to show significant anticancer activity against L1210, P388, S-180, and CCRF-CEM cells with ED50 values of 50, 5, 10, and 1 microM, respectively. None of these compounds demonstrated significant antiviral activity against HSV-1, HSV-2, or HIV-1. These compounds were also evaluated against thymidine kinases derived from HSV-I (strain KOS), HSV-2 (strain 333), and mammalian (K562) cells. The thymidine kinase (HSV-1 strain KOS) was inhibited significantly by both 3'-deoxy-3'-C-(hydroxymethyl)- and 3'-deoxy-3'-C-(fluoromethyl)thymidine.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm00055a006</identifier><identifier>PMID: 8381182</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Animals ; Antimetabolites, Antineoplastic - chemical synthesis ; Antimetabolites, Antineoplastic - pharmacology ; Antiviral Agents - chemical synthesis ; Antiviral Agents - pharmacology ; Deoxyribonucleosides - chemical synthesis ; Deoxyribonucleosides - pharmacology ; Dideoxynucleosides - chemical synthesis ; Dideoxynucleosides - pharmacology ; Drug Screening Assays, Antitumor ; HIV-1 - drug effects ; Humans ; Mice ; Simplexvirus - drug effects ; Thymidine Kinase - antagonists & inhibitors ; Tumor Cells, Cultured ; Zidovudine - analogs & derivatives ; Zidovudine - chemical synthesis ; Zidovudine - pharmacology</subject><ispartof>Journal of medicinal chemistry, 1993-02, Vol.36 (3), p.353-362</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a385t-6d1644338c6279a1edc88abfb31b39aff52ca718fe581bdedfc738d547d5a47d3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jm00055a006$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm00055a006$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8381182$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lin, Tai Shun</creatorcontrib><creatorcontrib>Zhu, Ju Liang</creatorcontrib><creatorcontrib>Dutschman, Ginger E</creatorcontrib><creatorcontrib>Cheng, Yung Chi</creatorcontrib><creatorcontrib>Prusoff, William H</creatorcontrib><title>Syntheses and biological evaluations of 3'-deoxy-3'-C-branched-chain-substituted nucleosides</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>Various 3'-deoxy-3'-C-(hydroxymethyl)-, 3'-deoxy-3'-C-(fluoromethyl)-, 3'-deoxy-3'-C-(azidomethyl)-, and 3'-deoxy-3'-C-(aminomethyl)-substituted nucleosides (total 12 compounds) have been synthesized and evaluated against L1210, P388, S-180, and CCRF-CEM cells and HSV-1, HSV-2, and HIV-1 in culture. Only 3'-deoxy-3'-C-(hydroxymethyl)thymidine (36) was found to show significant anticancer activity against L1210, P388, S-180, and CCRF-CEM cells with ED50 values of 50, 5, 10, and 1 microM, respectively. None of these compounds demonstrated significant antiviral activity against HSV-1, HSV-2, or HIV-1. These compounds were also evaluated against thymidine kinases derived from HSV-I (strain KOS), HSV-2 (strain 333), and mammalian (K562) cells. The thymidine kinase (HSV-1 strain KOS) was inhibited significantly by both 3'-deoxy-3'-C-(hydroxymethyl)- and 3'-deoxy-3'-C-(fluoromethyl)thymidine.</description><subject>Animals</subject><subject>Antimetabolites, Antineoplastic - chemical synthesis</subject><subject>Antimetabolites, Antineoplastic - pharmacology</subject><subject>Antiviral Agents - chemical synthesis</subject><subject>Antiviral Agents - pharmacology</subject><subject>Deoxyribonucleosides - chemical synthesis</subject><subject>Deoxyribonucleosides - pharmacology</subject><subject>Dideoxynucleosides - chemical synthesis</subject><subject>Dideoxynucleosides - pharmacology</subject><subject>Drug Screening Assays, Antitumor</subject><subject>HIV-1 - drug effects</subject><subject>Humans</subject><subject>Mice</subject><subject>Simplexvirus - drug effects</subject><subject>Thymidine Kinase - antagonists & inhibitors</subject><subject>Tumor Cells, Cultured</subject><subject>Zidovudine - analogs & derivatives</subject><subject>Zidovudine - chemical synthesis</subject><subject>Zidovudine - pharmacology</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkE1LHEEQhpuQYDbGU87CnOIhdOyP6ZneoyyJCgsKuxEPQlPTXeP2ZnZap2bE_feO7CIevFQVvA9vwcPYDyl-S6Hk6XojhDAGhCg-sYk0SvDcivwzmwihFFeF0l_ZN6L1iGmp9AE7sNpKadWE3S22bb9CQsqgDVkVU5Puo4cmwydoBuhjailLdaZPeMD0vOXjMeNVB61fYeB-BbHlNFTUx37oMWTt4BtMFAPSd_alhobwaL8P2b-_f5azCz6_Or-cnc05aGt6XgRZ5LnW1heqnILE4K2Fqq60rPQU6tooD6W0NRorq4Ch9qW2weRlMDAOfch-7nofuvQ4IPVuE8lj00CLaSAni6kRpdAj-GsH-i4RdVi7hy5uoNs6KdyrS_fO5Ugf72uHaoPhjd3LG3O-yyP1-PwWQ_ffFaUujVteL9zFcn6bny9u3GLkT3Y8eHLrNHTtKOXDzy8naYte</recordid><startdate>19930205</startdate><enddate>19930205</enddate><creator>Lin, Tai Shun</creator><creator>Zhu, Ju Liang</creator><creator>Dutschman, Ginger E</creator><creator>Cheng, Yung Chi</creator><creator>Prusoff, William H</creator><general>American Chemical Society</general><scope>BSCLL</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><scope>7TM</scope></search><sort><creationdate>19930205</creationdate><title>Syntheses and biological evaluations of 3'-deoxy-3'-C-branched-chain-substituted nucleosides</title><author>Lin, Tai Shun ; Zhu, Ju Liang ; Dutschman, Ginger E ; Cheng, Yung Chi ; Prusoff, William H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a385t-6d1644338c6279a1edc88abfb31b39aff52ca718fe581bdedfc738d547d5a47d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1993</creationdate><topic>Animals</topic><topic>Antimetabolites, Antineoplastic - chemical synthesis</topic><topic>Antimetabolites, Antineoplastic - pharmacology</topic><topic>Antiviral Agents - chemical synthesis</topic><topic>Antiviral Agents - pharmacology</topic><topic>Deoxyribonucleosides - chemical synthesis</topic><topic>Deoxyribonucleosides - pharmacology</topic><topic>Dideoxynucleosides - chemical synthesis</topic><topic>Dideoxynucleosides - pharmacology</topic><topic>Drug Screening Assays, Antitumor</topic><topic>HIV-1 - drug effects</topic><topic>Humans</topic><topic>Mice</topic><topic>Simplexvirus - drug effects</topic><topic>Thymidine Kinase - antagonists & inhibitors</topic><topic>Tumor Cells, Cultured</topic><topic>Zidovudine - analogs & derivatives</topic><topic>Zidovudine - chemical synthesis</topic><topic>Zidovudine - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lin, Tai Shun</creatorcontrib><creatorcontrib>Zhu, Ju Liang</creatorcontrib><creatorcontrib>Dutschman, Ginger E</creatorcontrib><creatorcontrib>Cheng, Yung Chi</creatorcontrib><creatorcontrib>Prusoff, William H</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lin, Tai Shun</au><au>Zhu, Ju Liang</au><au>Dutschman, Ginger E</au><au>Cheng, Yung Chi</au><au>Prusoff, William H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Syntheses and biological evaluations of 3'-deoxy-3'-C-branched-chain-substituted nucleosides</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>1993-02-05</date><risdate>1993</risdate><volume>36</volume><issue>3</issue><spage>353</spage><epage>362</epage><pages>353-362</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><abstract>Various 3'-deoxy-3'-C-(hydroxymethyl)-, 3'-deoxy-3'-C-(fluoromethyl)-, 3'-deoxy-3'-C-(azidomethyl)-, and 3'-deoxy-3'-C-(aminomethyl)-substituted nucleosides (total 12 compounds) have been synthesized and evaluated against L1210, P388, S-180, and CCRF-CEM cells and HSV-1, HSV-2, and HIV-1 in culture. Only 3'-deoxy-3'-C-(hydroxymethyl)thymidine (36) was found to show significant anticancer activity against L1210, P388, S-180, and CCRF-CEM cells with ED50 values of 50, 5, 10, and 1 microM, respectively. None of these compounds demonstrated significant antiviral activity against HSV-1, HSV-2, or HIV-1. These compounds were also evaluated against thymidine kinases derived from HSV-I (strain KOS), HSV-2 (strain 333), and mammalian (K562) cells. The thymidine kinase (HSV-1 strain KOS) was inhibited significantly by both 3'-deoxy-3'-C-(hydroxymethyl)- and 3'-deoxy-3'-C-(fluoromethyl)thymidine.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>8381182</pmid><doi>10.1021/jm00055a006</doi><tpages>10</tpages></addata></record> |
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| source | ACS Publications; MEDLINE |
| subjects | Animals Antimetabolites, Antineoplastic - chemical synthesis Antimetabolites, Antineoplastic - pharmacology Antiviral Agents - chemical synthesis Antiviral Agents - pharmacology Deoxyribonucleosides - chemical synthesis Deoxyribonucleosides - pharmacology Dideoxynucleosides - chemical synthesis Dideoxynucleosides - pharmacology Drug Screening Assays, Antitumor HIV-1 - drug effects Humans Mice Simplexvirus - drug effects Thymidine Kinase - antagonists & inhibitors Tumor Cells, Cultured Zidovudine - analogs & derivatives Zidovudine - chemical synthesis Zidovudine - pharmacology |
| title | Syntheses and biological evaluations of 3'-deoxy-3'-C-branched-chain-substituted nucleosides |
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