Decomposition Pathways and in Vitro HIV Inhibitory Effects of IsoddA Pronucleotides: Toward a Rational Approach for Intracellular Delivery of Nucleoside 5‘-Monophosphates
The decomposition pathways and kinetics in various biological media and the in vitro anti-HIV-1 and anti-HIV-2 activities of four derivatives of the 5‘-mononucleotide of isoddA incorporating carboxylate esterase-labile transient phosphate protecting groups are reported and compared: namely, two mon...
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| Veröffentlicht in: | Journal of medicinal chemistry 1996-05, Vol.39 (10), p.1981-1990 |
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| container_end_page | 1990 |
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| container_issue | 10 |
| container_start_page | 1981 |
| container_title | Journal of medicinal chemistry |
| container_volume | 39 |
| creator | Valette, Gilles Pompon, Alain Girardet, Jean-Luc Cappellacci, Loredana Franchetti, Palmarisa Grifantini, Mario La Colla, Paolo Loi, Anna Giulia Périgaud, Christian Gosselin, Gilles Imbach, Jean-Louis |
| description | The decomposition pathways and kinetics in various biological media and the in vitro anti-HIV-1 and anti-HIV-2 activities of four derivatives of the 5‘-mononucleotide of isoddA incorporating carboxylate esterase-labile transient phosphate protecting groups are reported and compared: namely, two mononucleoside aryl phosphoramidate derivatives 1a,b and two mononucleoside phosphotriester derivatives incorporating two S-acyl-2-thioethyl groups 2a,b. All four compounds show better antiviral activity, compared to the parent nucleoside analog isoddA. The results highlight that both types of compounds act as pronucleotides, i.e. they exert their antiviral effect via intracellular delivery of the 5‘-mononucleotide of isoddA. The results may give insights for the design of new more efficient pronucleotides. |
| doi_str_mv | 10.1021/jm9507338 |
| format | Article |
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All four compounds show better antiviral activity, compared to the parent nucleoside analog isoddA. The results highlight that both types of compounds act as pronucleotides, i.e. they exert their antiviral effect via intracellular delivery of the 5‘-mononucleotide of isoddA. The results may give insights for the design of new more efficient pronucleotides.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm9507338</identifier><identifier>PMID: 8642557</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>AIDS/HIV ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiviral agents ; Biological and medical sciences ; Cell Line ; Dideoxyadenosine - analogs & derivatives ; Dideoxyadenosine - chemistry ; Dideoxyadenosine - pharmacology ; HIV-1 - drug effects ; HIV-2 - drug effects ; human immunodeficiency virus ; Humans ; Kinetics ; Magnetic Resonance Spectroscopy ; Medical sciences ; Nucleotides - chemistry ; Pharmacology. Drug treatments ; Spectrometry, Mass, Fast Atom Bombardment</subject><ispartof>Journal of medicinal chemistry, 1996-05, Vol.39 (10), p.1981-1990</ispartof><rights>Copyright © 1996 American Chemical Society</rights><rights>1996 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a408t-d9cd56417f1a29b3e2d10a5f35041315ba9c05b61b119bc2a87bfc33cdd3e073</citedby><cites>FETCH-LOGICAL-a408t-d9cd56417f1a29b3e2d10a5f35041315ba9c05b61b119bc2a87bfc33cdd3e073</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/jm9507338$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm9507338$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3088260$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8642557$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Valette, Gilles</creatorcontrib><creatorcontrib>Pompon, Alain</creatorcontrib><creatorcontrib>Girardet, Jean-Luc</creatorcontrib><creatorcontrib>Cappellacci, Loredana</creatorcontrib><creatorcontrib>Franchetti, Palmarisa</creatorcontrib><creatorcontrib>Grifantini, Mario</creatorcontrib><creatorcontrib>La Colla, Paolo</creatorcontrib><creatorcontrib>Loi, Anna Giulia</creatorcontrib><creatorcontrib>Périgaud, Christian</creatorcontrib><creatorcontrib>Gosselin, Gilles</creatorcontrib><creatorcontrib>Imbach, Jean-Louis</creatorcontrib><title>Decomposition Pathways and in Vitro HIV Inhibitory Effects of IsoddA Pronucleotides: Toward a Rational Approach for Intracellular Delivery of Nucleoside 5‘-Monophosphates</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>The decomposition pathways and kinetics in various biological media and the in vitro anti-HIV-1 and anti-HIV-2 activities of four derivatives of the 5‘-mononucleotide of isoddA incorporating carboxylate esterase-labile transient phosphate protecting groups are reported and compared: namely, two mononucleoside aryl phosphoramidate derivatives 1a,b and two mononucleoside phosphotriester derivatives incorporating two S-acyl-2-thioethyl groups 2a,b. All four compounds show better antiviral activity, compared to the parent nucleoside analog isoddA. The results highlight that both types of compounds act as pronucleotides, i.e. they exert their antiviral effect via intracellular delivery of the 5‘-mononucleotide of isoddA. The results may give insights for the design of new more efficient pronucleotides.</description><subject>AIDS/HIV</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiviral agents</subject><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>Dideoxyadenosine - analogs & derivatives</subject><subject>Dideoxyadenosine - chemistry</subject><subject>Dideoxyadenosine - pharmacology</subject><subject>HIV-1 - drug effects</subject><subject>HIV-2 - drug effects</subject><subject>human immunodeficiency virus</subject><subject>Humans</subject><subject>Kinetics</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Medical sciences</subject><subject>Nucleotides - chemistry</subject><subject>Pharmacology. Drug treatments</subject><subject>Spectrometry, Mass, Fast Atom Bombardment</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctuEzEUhkcIVNLCggdA8gIqsRjwZTwXdqEXGlFCBFG31hnbozjMjAfbQ8muW96At-Cd-iQ4JMoKidVZ_J8-_Tp_kjwj-DXBlLxZdxXHBWPlg2RCOMVpVuLsYTLBmNKU5pQ9To69X2OMGaHsKDkq84xyXkyS3-da2m6w3gRje7SAsLqFjUfQK2R6dGOCs-hqdoNm_crUJli3QRdNo2XwyDZo5q1SU7Rwth9lq20wSvu393c_0dLeglMI0GfYmqFF02FwFuQKNdZFXXAgdduOLTh0rlvzXUd1VM7_inwUIX5_9yv9aHs7rKwfVhC0f5I8aqD1-un-niTLy4vl2VV6_en97Gx6nUKGy5CqSiqeZ6RoCNCqZpoqgoE3jOOMMMJrqCTmdU5qQqpaUiiLupGMSaWYjp88SU532lj526h9EJ3x27rQazt6UZSYFTmp_gsSzvOi4iSCr3agdNZ7pxsxONOB2wiCxXZEcRgxss_30rHutDqQ-9Vi_mKfg5fQNg56afwBY7gsaY4jlu4w44P-cYjBfRV5wQoulosvYlF-mL8jl5mYR_7ljgfpxdqOLq7m_1HvD0dQwu8</recordid><startdate>19960510</startdate><enddate>19960510</enddate><creator>Valette, Gilles</creator><creator>Pompon, Alain</creator><creator>Girardet, Jean-Luc</creator><creator>Cappellacci, Loredana</creator><creator>Franchetti, Palmarisa</creator><creator>Grifantini, Mario</creator><creator>La Colla, Paolo</creator><creator>Loi, Anna Giulia</creator><creator>Périgaud, Christian</creator><creator>Gosselin, Gilles</creator><creator>Imbach, Jean-Louis</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><scope>7TM</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>19960510</creationdate><title>Decomposition Pathways and in Vitro HIV Inhibitory Effects of IsoddA Pronucleotides: Toward a Rational Approach for Intracellular Delivery of Nucleoside 5‘-Monophosphates</title><author>Valette, Gilles ; Pompon, Alain ; Girardet, Jean-Luc ; Cappellacci, Loredana ; Franchetti, Palmarisa ; Grifantini, Mario ; La Colla, Paolo ; Loi, Anna Giulia ; Périgaud, Christian ; Gosselin, Gilles ; Imbach, Jean-Louis</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a408t-d9cd56417f1a29b3e2d10a5f35041315ba9c05b61b119bc2a87bfc33cdd3e073</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>AIDS/HIV</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antiviral agents</topic><topic>Biological and medical sciences</topic><topic>Cell Line</topic><topic>Dideoxyadenosine - analogs & derivatives</topic><topic>Dideoxyadenosine - chemistry</topic><topic>Dideoxyadenosine - pharmacology</topic><topic>HIV-1 - drug effects</topic><topic>HIV-2 - drug effects</topic><topic>human immunodeficiency virus</topic><topic>Humans</topic><topic>Kinetics</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Medical sciences</topic><topic>Nucleotides - chemistry</topic><topic>Pharmacology. Drug treatments</topic><topic>Spectrometry, Mass, Fast Atom Bombardment</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Valette, Gilles</creatorcontrib><creatorcontrib>Pompon, Alain</creatorcontrib><creatorcontrib>Girardet, Jean-Luc</creatorcontrib><creatorcontrib>Cappellacci, Loredana</creatorcontrib><creatorcontrib>Franchetti, Palmarisa</creatorcontrib><creatorcontrib>Grifantini, Mario</creatorcontrib><creatorcontrib>La Colla, Paolo</creatorcontrib><creatorcontrib>Loi, Anna Giulia</creatorcontrib><creatorcontrib>Périgaud, Christian</creatorcontrib><creatorcontrib>Gosselin, Gilles</creatorcontrib><creatorcontrib>Imbach, Jean-Louis</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><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Valette, Gilles</au><au>Pompon, Alain</au><au>Girardet, Jean-Luc</au><au>Cappellacci, Loredana</au><au>Franchetti, Palmarisa</au><au>Grifantini, Mario</au><au>La Colla, Paolo</au><au>Loi, Anna Giulia</au><au>Périgaud, Christian</au><au>Gosselin, Gilles</au><au>Imbach, Jean-Louis</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Decomposition Pathways and in Vitro HIV Inhibitory Effects of IsoddA Pronucleotides: Toward a Rational Approach for Intracellular Delivery of Nucleoside 5‘-Monophosphates</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>1996-05-10</date><risdate>1996</risdate><volume>39</volume><issue>10</issue><spage>1981</spage><epage>1990</epage><pages>1981-1990</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>The decomposition pathways and kinetics in various biological media and the in vitro anti-HIV-1 and anti-HIV-2 activities of four derivatives of the 5‘-mononucleotide of isoddA incorporating carboxylate esterase-labile transient phosphate protecting groups are reported and compared: namely, two mononucleoside aryl phosphoramidate derivatives 1a,b and two mononucleoside phosphotriester derivatives incorporating two S-acyl-2-thioethyl groups 2a,b. All four compounds show better antiviral activity, compared to the parent nucleoside analog isoddA. The results highlight that both types of compounds act as pronucleotides, i.e. they exert their antiviral effect via intracellular delivery of the 5‘-mononucleotide of isoddA. The results may give insights for the design of new more efficient pronucleotides.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>8642557</pmid><doi>10.1021/jm9507338</doi><tpages>10</tpages></addata></record> |
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| identifier | ISSN: 0022-2623 |
| ispartof | Journal of medicinal chemistry, 1996-05, Vol.39 (10), p.1981-1990 |
| issn | 0022-2623 1520-4804 |
| language | eng |
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| source | ACS Publications; MEDLINE |
| subjects | AIDS/HIV Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Biological and medical sciences Cell Line Dideoxyadenosine - analogs & derivatives Dideoxyadenosine - chemistry Dideoxyadenosine - pharmacology HIV-1 - drug effects HIV-2 - drug effects human immunodeficiency virus Humans Kinetics Magnetic Resonance Spectroscopy Medical sciences Nucleotides - chemistry Pharmacology. Drug treatments Spectrometry, Mass, Fast Atom Bombardment |
| title | Decomposition Pathways and in Vitro HIV Inhibitory Effects of IsoddA Pronucleotides: Toward a Rational Approach for Intracellular Delivery of Nucleoside 5‘-Monophosphates |
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