Synthesis and Antiviral Evaluation of (1,4-Disubstituted-1,2,3-Triazol)-(<i>E</i>)-2-Methyl-but-2-Enyl Nucleoside Phosphonate Prodrugs
A series of hitherto unknown (1,4-disubstituted-1,2,3-triazol)-(<i>E</i>)-2-methyl-but-2-enyl nucleosides phosphonate prodrugs bearing 4-substituted-1,2,3-triazoles were prepared in a straight approach through an olefin acyclic cross metathesis as the key synthetic step. All novel compou...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/5/1493 |
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| author | Tuniyazi Abuduaini Vincent Roy Julien Marlet Catherine Gaudy-Graffin Denys Brand Cécile Baronti Franck Touret Bruno Coutard Tamara R. McBrayer Raymond F. Schinazi Luigi A. Agrofoglio |
| author_facet | Tuniyazi Abuduaini Vincent Roy Julien Marlet Catherine Gaudy-Graffin Denys Brand Cécile Baronti Franck Touret Bruno Coutard Tamara R. McBrayer Raymond F. Schinazi Luigi A. Agrofoglio |
| author_sort | Tuniyazi Abuduaini |
| collection | DOAJ |
| description | A series of hitherto unknown (1,4-disubstituted-1,2,3-triazol)-(<i>E</i>)-2-methyl-but-2-enyl nucleosides phosphonate prodrugs bearing 4-substituted-1,2,3-triazoles were prepared in a straight approach through an olefin acyclic cross metathesis as the key synthetic step. All novel compounds were evaluated for their antiviral activities against HBV, HIV and SARS-CoV-2. Among these molecules, only compound <b>15j</b>, a hexadecyloxypropyl (HDP)/(<i>isopropyloxycarbonyl</i>-oxymethyl)-ester (POC) prodrug, showed activity against HBV in Huh7 cell cultures with 62% inhibition at 10 μM, without significant cytotoxicity (IC<sub>50</sub> = 66.4 μM in HepG2 cells, IC<sub>50</sub> = 43.1 μM in HepG2 cells) at 10 μM. |
| first_indexed | 2024-03-10T13:24:13Z |
| format | Article |
| id | doaj.art-7ab16fe8f4df4357a67e0e3149ef7bfa |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T13:24:13Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-7ab16fe8f4df4357a67e0e3149ef7bfa2023-11-21T09:47:41ZengMDPI AGMolecules1420-30492021-03-01265149310.3390/molecules26051493Synthesis and Antiviral Evaluation of (1,4-Disubstituted-1,2,3-Triazol)-(<i>E</i>)-2-Methyl-but-2-Enyl Nucleoside Phosphonate ProdrugsTuniyazi Abuduaini0Vincent Roy1Julien Marlet2Catherine Gaudy-Graffin3Denys Brand4Cécile Baronti5Franck Touret6Bruno Coutard7Tamara R. McBrayer8Raymond F. Schinazi9Luigi A. Agrofoglio10Institute of Organic and Analytical Chemistry, CNRS UMR 7311, Universite d’Orléans, F-45067 Orléans, FranceInstitute of Organic and Analytical Chemistry, CNRS UMR 7311, Universite d’Orléans, F-45067 Orléans, FranceInserm U1259, Université de Tours, 37032 Tours, FranceInserm U1259, Université de Tours, 37032 Tours, FranceInserm U1259, Université de Tours, 37032 Tours, FranceUnité des Virus Émergents (UVE: Aix-Marseille Univ, IRD 190, Inserm 1207, IHU Méditerranée Infection), 13000 Marseille, FranceUnité des Virus Émergents (UVE: Aix-Marseille Univ, IRD 190, Inserm 1207, IHU Méditerranée Infection), 13000 Marseille, FranceUnité des Virus Émergents (UVE: Aix-Marseille Univ, IRD 190, Inserm 1207, IHU Méditerranée Infection), 13000 Marseille, FranceCenter for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, GA 30222, USACenter for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, GA 30222, USAInstitute of Organic and Analytical Chemistry, CNRS UMR 7311, Universite d’Orléans, F-45067 Orléans, FranceA series of hitherto unknown (1,4-disubstituted-1,2,3-triazol)-(<i>E</i>)-2-methyl-but-2-enyl nucleosides phosphonate prodrugs bearing 4-substituted-1,2,3-triazoles were prepared in a straight approach through an olefin acyclic cross metathesis as the key synthetic step. All novel compounds were evaluated for their antiviral activities against HBV, HIV and SARS-CoV-2. Among these molecules, only compound <b>15j</b>, a hexadecyloxypropyl (HDP)/(<i>isopropyloxycarbonyl</i>-oxymethyl)-ester (POC) prodrug, showed activity against HBV in Huh7 cell cultures with 62% inhibition at 10 μM, without significant cytotoxicity (IC<sub>50</sub> = 66.4 μM in HepG2 cells, IC<sub>50</sub> = 43.1 μM in HepG2 cells) at 10 μM.https://www.mdpi.com/1420-3049/26/5/1493nucleosidesolefin cross metathesisultrasoundcopper-catalyzed azide-alkyne cycloaddition (CuAAC)antiviral propertiesHBV |
| spellingShingle | Tuniyazi Abuduaini Vincent Roy Julien Marlet Catherine Gaudy-Graffin Denys Brand Cécile Baronti Franck Touret Bruno Coutard Tamara R. McBrayer Raymond F. Schinazi Luigi A. Agrofoglio Synthesis and Antiviral Evaluation of (1,4-Disubstituted-1,2,3-Triazol)-(<i>E</i>)-2-Methyl-but-2-Enyl Nucleoside Phosphonate Prodrugs Molecules nucleosides olefin cross metathesis ultrasound copper-catalyzed azide-alkyne cycloaddition (CuAAC) antiviral properties HBV |
| title | Synthesis and Antiviral Evaluation of (1,4-Disubstituted-1,2,3-Triazol)-(<i>E</i>)-2-Methyl-but-2-Enyl Nucleoside Phosphonate Prodrugs |
| title_full | Synthesis and Antiviral Evaluation of (1,4-Disubstituted-1,2,3-Triazol)-(<i>E</i>)-2-Methyl-but-2-Enyl Nucleoside Phosphonate Prodrugs |
| title_fullStr | Synthesis and Antiviral Evaluation of (1,4-Disubstituted-1,2,3-Triazol)-(<i>E</i>)-2-Methyl-but-2-Enyl Nucleoside Phosphonate Prodrugs |
| title_full_unstemmed | Synthesis and Antiviral Evaluation of (1,4-Disubstituted-1,2,3-Triazol)-(<i>E</i>)-2-Methyl-but-2-Enyl Nucleoside Phosphonate Prodrugs |
| title_short | Synthesis and Antiviral Evaluation of (1,4-Disubstituted-1,2,3-Triazol)-(<i>E</i>)-2-Methyl-but-2-Enyl Nucleoside Phosphonate Prodrugs |
| title_sort | synthesis and antiviral evaluation of 1 4 disubstituted 1 2 3 triazol i e i 2 methyl but 2 enyl nucleoside phosphonate prodrugs |
| topic | nucleosides olefin cross metathesis ultrasound copper-catalyzed azide-alkyne cycloaddition (CuAAC) antiviral properties HBV |
| url | https://www.mdpi.com/1420-3049/26/5/1493 |
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