Activity of the (R)-Enantiomers of 9-(2-Phosphonylmethoxypropyl)-Adenine and 9-(2-Phosphonylmethoxypropyl)-2,6-diaminopurine against Human Immunodeficiency Virus in Different Human Cell Systems
The (S)- and (R)-enantiomers of 9-(2-phosphonylmethoxypropyl) derivatives of adenine (PMPA) and 2,6-diaminopurine (PMPDAP) were evaluated for their inhibitory effect on HIV replication in several human cell systems, including natural peripheral blood lymphocytes (PBL) and freshly isolated monocyte/m...
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| Veröffentlicht in: | Biochemical and biophysical research communications 1996-02, Vol.219 (2), p.337-341 |
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| container_title | Biochemical and biophysical research communications |
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| creator | Balzarini, J. Aquaro, S. Perno, C.-F. Witvrouw, M. Holý, A. De Clercq, E. |
| description | The (S)- and (R)-enantiomers of 9-(2-phosphonylmethoxypropyl) derivatives of adenine (PMPA) and 2,6-diaminopurine (PMPDAP) were evaluated for their inhibitory effect on HIV replication in several human cell systems, including natural peripheral blood lymphocytes (PBL) and freshly isolated monocyte/macrophages (M/M). The (R)-enantiomers of PMPDAP and PMPA were ∼10- to 100-fold more effective against HIV than their (S)-enantiomeric counterparts. The antiviral efficacy of (R)-PMPA was comparable to that of the prototype acyclic nucleoside phosphonate 9-(2-phosphonylmethoxyethyl)adenine (PMEA). The most potent and selective HIV inhibitor was (R)-PMPDAP. Its 50% effective concentration ranged from 0.01 μM for HIV-1/Ba-L in M/M to 1–2.8 μM for HIV-1/IIIBand HIV-1/HE in C8166, CEM, Molt/4, MT-4 and PBL cells. Both (R)-PMPA and (R)-PMPDAP were not toxic to the host cells at 300 μM. |
| doi_str_mv | 10.1006/bbrc.1996.0234 |
| format | Article |
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The (R)-enantiomers of PMPDAP and PMPA were ∼10- to 100-fold more effective against HIV than their (S)-enantiomeric counterparts. The antiviral efficacy of (R)-PMPA was comparable to that of the prototype acyclic nucleoside phosphonate 9-(2-phosphonylmethoxyethyl)adenine (PMEA). The most potent and selective HIV inhibitor was (R)-PMPDAP. Its 50% effective concentration ranged from 0.01 μM for HIV-1/Ba-L in M/M to 1–2.8 μM for HIV-1/IIIBand HIV-1/HE in C8166, CEM, Molt/4, MT-4 and PBL cells. 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The (R)-enantiomers of PMPDAP and PMPA were ∼10- to 100-fold more effective against HIV than their (S)-enantiomeric counterparts. The antiviral efficacy of (R)-PMPA was comparable to that of the prototype acyclic nucleoside phosphonate 9-(2-phosphonylmethoxyethyl)adenine (PMEA). The most potent and selective HIV inhibitor was (R)-PMPDAP. Its 50% effective concentration ranged from 0.01 μM for HIV-1/Ba-L in M/M to 1–2.8 μM for HIV-1/IIIBand HIV-1/HE in C8166, CEM, Molt/4, MT-4 and PBL cells. Both (R)-PMPA and (R)-PMPDAP were not toxic to the host cells at 300 μM.</description><subject>Adenine - analogs & derivatives</subject><subject>Adenine - pharmacology</subject><subject>Antiviral Agents - pharmacology</subject><subject>Cell Line</subject><subject>Dose-Response Relationship, Drug</subject><subject>HIV-1 - drug effects</subject><subject>Humans</subject><subject>Organophosphonates</subject><subject>Organophosphorus Compounds - pharmacology</subject><subject>Soman - analogs & derivatives</subject><subject>Soman - pharmacology</subject><subject>Stereoisomerism</subject><subject>Structure-Activity Relationship</subject><subject>Virus Replication - drug effects</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkVFrFDEUhYMo7bb66puQxxbMmsxk08njslZbKCitLb4N2cmNmzJJhiRTnJ_nP2umW30rPl3I-c7l5hyE3jO6ZJSKT9tt7JZMSrGkVc1foQWjkpKKUf4aLWghSCXZz0N0lNI9pYxxIQ_QQSMol02zQH_WXbYPNk84GJx3gE-uT8m5Vz7b4CCm-VmSk4p834U07IKfegd5F35PQwzD1J-StQZvPWDl9X_I6qMg2ipnfRjG-OT5paxPGV-MTnl86dzogwZjOwu-m_CdjWPC1uPP1hiI4P-SG-h7fDOlDC69RW-M6hO8e57H6PbL-Y_NBbn69vVys74iXV3LTMSKMVBMK1GBMZ3ilNNG1FwZKktCivNVo1e6BGZqTXklZKFpY6ozWaSS7TFa7vd2MaQUwbRDtE7FqWW0nato5yrauYp2rqIYPuwNw7h1oP_hz9kXvdnrUK5-sBDb9PRv0DZCl1sd7EurHwGEtprH</recordid><startdate>19960215</startdate><enddate>19960215</enddate><creator>Balzarini, J.</creator><creator>Aquaro, S.</creator><creator>Perno, C.-F.</creator><creator>Witvrouw, M.</creator><creator>Holý, A.</creator><creator>De Clercq, E.</creator><general>Elsevier Inc</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></search><sort><creationdate>19960215</creationdate><title>Activity of the (R)-Enantiomers of 9-(2-Phosphonylmethoxypropyl)-Adenine and 9-(2-Phosphonylmethoxypropyl)-2,6-diaminopurine against Human Immunodeficiency Virus in Different Human Cell Systems</title><author>Balzarini, J. ; Aquaro, S. ; Perno, C.-F. ; Witvrouw, M. ; Holý, A. ; De Clercq, E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c339t-6511ea1da62effca40408634af09291a4458d5d006f3d04269ea108f279445023</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Adenine - analogs & derivatives</topic><topic>Adenine - pharmacology</topic><topic>Antiviral Agents - pharmacology</topic><topic>Cell Line</topic><topic>Dose-Response Relationship, Drug</topic><topic>HIV-1 - drug effects</topic><topic>Humans</topic><topic>Organophosphonates</topic><topic>Organophosphorus Compounds - pharmacology</topic><topic>Soman - analogs & derivatives</topic><topic>Soman - pharmacology</topic><topic>Stereoisomerism</topic><topic>Structure-Activity Relationship</topic><topic>Virus Replication - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Balzarini, J.</creatorcontrib><creatorcontrib>Aquaro, S.</creatorcontrib><creatorcontrib>Perno, C.-F.</creatorcontrib><creatorcontrib>Witvrouw, M.</creatorcontrib><creatorcontrib>Holý, A.</creatorcontrib><creatorcontrib>De Clercq, E.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Balzarini, J.</au><au>Aquaro, S.</au><au>Perno, C.-F.</au><au>Witvrouw, M.</au><au>Holý, A.</au><au>De Clercq, E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activity of the (R)-Enantiomers of 9-(2-Phosphonylmethoxypropyl)-Adenine and 9-(2-Phosphonylmethoxypropyl)-2,6-diaminopurine against Human Immunodeficiency Virus in Different Human Cell Systems</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>1996-02-15</date><risdate>1996</risdate><volume>219</volume><issue>2</issue><spage>337</spage><epage>341</epage><pages>337-341</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>The (S)- and (R)-enantiomers of 9-(2-phosphonylmethoxypropyl) derivatives of adenine (PMPA) and 2,6-diaminopurine (PMPDAP) were evaluated for their inhibitory effect on HIV replication in several human cell systems, including natural peripheral blood lymphocytes (PBL) and freshly isolated monocyte/macrophages (M/M). The (R)-enantiomers of PMPDAP and PMPA were ∼10- to 100-fold more effective against HIV than their (S)-enantiomeric counterparts. The antiviral efficacy of (R)-PMPA was comparable to that of the prototype acyclic nucleoside phosphonate 9-(2-phosphonylmethoxyethyl)adenine (PMEA). The most potent and selective HIV inhibitor was (R)-PMPDAP. Its 50% effective concentration ranged from 0.01 μM for HIV-1/Ba-L in M/M to 1–2.8 μM for HIV-1/IIIBand HIV-1/HE in C8166, CEM, Molt/4, MT-4 and PBL cells. Both (R)-PMPA and (R)-PMPDAP were not toxic to the host cells at 300 μM.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>8604988</pmid><doi>10.1006/bbrc.1996.0234</doi><tpages>5</tpages></addata></record> |
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| ispartof | Biochemical and biophysical research communications, 1996-02, Vol.219 (2), p.337-341 |
| issn | 0006-291X 1090-2104 |
| language | eng |
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| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Adenine - analogs & derivatives Adenine - pharmacology Antiviral Agents - pharmacology Cell Line Dose-Response Relationship, Drug HIV-1 - drug effects Humans Organophosphonates Organophosphorus Compounds - pharmacology Soman - analogs & derivatives Soman - pharmacology Stereoisomerism Structure-Activity Relationship Virus Replication - drug effects |
| title | Activity of the (R)-Enantiomers of 9-(2-Phosphonylmethoxypropyl)-Adenine and 9-(2-Phosphonylmethoxypropyl)-2,6-diaminopurine against Human Immunodeficiency Virus in Different Human Cell Systems |
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