New HSV-1 Anti-Viral 1′-Homocarbocyclic Nucleoside Analogs with an Optically Active Substituted Bicyclo[2.2.1]Heptane Fragment as a Glycoside Moiety
New 1′-homocarbanucleoside analogs with an optically active substituted bicyclo[2.2.1]heptane skeleton as sugar moiety were synthesized. The pyrimidine analogs with uracil, 5-fluorouracil, thymine and cytosine and key intermediate with 6-chloropurine (<b>5</b>) as nucleobases w...
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| Language: | English |
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MDPI AG
2019-07-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/24/13/2446 |
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doaj-a989a1e4aea04f89899d8f01aae61e052020-11-25T02:45:32ZengMDPI AGMolecules1420-30492019-07-012413244610.3390/molecules24132446molecules24132446New HSV-1 Anti-Viral 1′-Homocarbocyclic Nucleoside Analogs with an Optically Active Substituted Bicyclo[2.2.1]Heptane Fragment as a Glycoside MoietyConstantin I. Tănase0Constantin Drăghici1Anamaria Hanganu2Lucia Pintilie3Maria Maganu4Alexandrina Volobueva5Ekaterina Sinegubova6Vladimir V. Zarubaev7Johan Neyts8Dirk Jochmans9Alexander V. Slita10National Institute for Chemical-Pharmaceutical Research and Development, Department of Bioactive Substances and Pharmaceutical Technologies, 112 Vitan Av., 031299 Bucharest-3, RomaniaOrganic Chemistry Center “C.D.Nenitescu”, Spectroscopy Laboratory, 202 B Splaiul Independentei, 060023 Bucharest, RomaniaOrganic Chemistry Center “C.D.Nenitescu”, Spectroscopy Laboratory, 202 B Splaiul Independentei, 060023 Bucharest, RomaniaNational Institute for Chemical-Pharmaceutical Research and Development, Department of Bioactive Substances and Pharmaceutical Technologies, 112 Vitan Av., 031299 Bucharest-3, RomaniaOrganic Chemistry Center “C.D.Nenitescu”, Spectroscopy Laboratory, 202 B Splaiul Independentei, 060023 Bucharest, RomaniaDepartment of Virology, Pasteur Institute of Epidemiology and Microbiology, 197101 St. Petersburg, RussiaDepartment of Virology, Pasteur Institute of Epidemiology and Microbiology, 197101 St. Petersburg, RussiaDepartment of Virology, Pasteur Institute of Epidemiology and Microbiology, 197101 St. Petersburg, RussiaKU Leuven Department of Micobiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Herestraat 49, BE-3000 Leuven, BelgiumKU Leuven Department of Micobiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Herestraat 49, BE-3000 Leuven, BelgiumKU Leuven Department of Micobiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Herestraat 49, BE-3000 Leuven, BelgiumNew 1′-homocarbanucleoside analogs with an optically active substituted bicyclo[2.2.1]heptane skeleton as sugar moiety were synthesized. The pyrimidine analogs with uracil, 5-fluorouracil, thymine and cytosine and key intermediate with 6-chloropurine (<b>5</b>) as nucleobases were synthesized by a selective Mitsunobu reaction on the primary hydroxymethyl group in the presence of 5-endo-hydroxyl group. Adenine and 6-substituted adenine homonucleosides were obtained by the substitution of the 6-chlorine atom of the key intermediate <b>5</b> with ammonia and selected amines, and 6-methoxy- and 6-ethoxy substituted purine homonucleosides by reaction with the corresponding alkoxides. No derivatives appeared active against entero, yellow fever, chikungunya, and adeno type 1viruses. Two compounds (<b>6j</b> and <b>6d</b>) had lower IC<sub>50</sub> (15 ± 2 and 21 ± 4 µM) and compound <b>6f</b> had an identical value of IC<sub>50</sub> (28 ± 4 µM) to that of acyclovir, suggesting that the bicyclo[2.2.1]heptane skeleton could be further studied to find a candidate for sugar moiety of the nucleosides.https://www.mdpi.com/1420-3049/24/13/24461′-homocarbonucleosidesbicyclo[2.2.1]heptane nucleosides6-chloropurine6-substituted adenine nucleosidesantiviral activityherpesvirusesmolecular docking |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Constantin I. Tănase Constantin Drăghici Anamaria Hanganu Lucia Pintilie Maria Maganu Alexandrina Volobueva Ekaterina Sinegubova Vladimir V. Zarubaev Johan Neyts Dirk Jochmans Alexander V. Slita |
| spellingShingle |
Constantin I. Tănase Constantin Drăghici Anamaria Hanganu Lucia Pintilie Maria Maganu Alexandrina Volobueva Ekaterina Sinegubova Vladimir V. Zarubaev Johan Neyts Dirk Jochmans Alexander V. Slita New HSV-1 Anti-Viral 1′-Homocarbocyclic Nucleoside Analogs with an Optically Active Substituted Bicyclo[2.2.1]Heptane Fragment as a Glycoside Moiety Molecules 1′-homocarbonucleosides bicyclo[2.2.1]heptane nucleosides 6-chloropurine 6-substituted adenine nucleosides antiviral activity herpesviruses molecular docking |
| author_facet |
Constantin I. Tănase Constantin Drăghici Anamaria Hanganu Lucia Pintilie Maria Maganu Alexandrina Volobueva Ekaterina Sinegubova Vladimir V. Zarubaev Johan Neyts Dirk Jochmans Alexander V. Slita |
| author_sort |
Constantin I. Tănase |
| title |
New HSV-1 Anti-Viral 1′-Homocarbocyclic Nucleoside Analogs with an Optically Active Substituted Bicyclo[2.2.1]Heptane Fragment as a Glycoside Moiety |
| title_short |
New HSV-1 Anti-Viral 1′-Homocarbocyclic Nucleoside Analogs with an Optically Active Substituted Bicyclo[2.2.1]Heptane Fragment as a Glycoside Moiety |
| title_full |
New HSV-1 Anti-Viral 1′-Homocarbocyclic Nucleoside Analogs with an Optically Active Substituted Bicyclo[2.2.1]Heptane Fragment as a Glycoside Moiety |
| title_fullStr |
New HSV-1 Anti-Viral 1′-Homocarbocyclic Nucleoside Analogs with an Optically Active Substituted Bicyclo[2.2.1]Heptane Fragment as a Glycoside Moiety |
| title_full_unstemmed |
New HSV-1 Anti-Viral 1′-Homocarbocyclic Nucleoside Analogs with an Optically Active Substituted Bicyclo[2.2.1]Heptane Fragment as a Glycoside Moiety |
| title_sort |
new hsv-1 anti-viral 1′-homocarbocyclic nucleoside analogs with an optically active substituted bicyclo[2.2.1]heptane fragment as a glycoside moiety |
| publisher |
MDPI AG |
| series |
Molecules |
| issn |
1420-3049 |
| publishDate |
2019-07-01 |
| description |
New 1′-homocarbanucleoside analogs with an optically active substituted bicyclo[2.2.1]heptane skeleton as sugar moiety were synthesized. The pyrimidine analogs with uracil, 5-fluorouracil, thymine and cytosine and key intermediate with 6-chloropurine (<b>5</b>) as nucleobases were synthesized by a selective Mitsunobu reaction on the primary hydroxymethyl group in the presence of 5-endo-hydroxyl group. Adenine and 6-substituted adenine homonucleosides were obtained by the substitution of the 6-chlorine atom of the key intermediate <b>5</b> with ammonia and selected amines, and 6-methoxy- and 6-ethoxy substituted purine homonucleosides by reaction with the corresponding alkoxides. No derivatives appeared active against entero, yellow fever, chikungunya, and adeno type 1viruses. Two compounds (<b>6j</b> and <b>6d</b>) had lower IC<sub>50</sub> (15 ± 2 and 21 ± 4 µM) and compound <b>6f</b> had an identical value of IC<sub>50</sub> (28 ± 4 µM) to that of acyclovir, suggesting that the bicyclo[2.2.1]heptane skeleton could be further studied to find a candidate for sugar moiety of the nucleosides. |
| topic |
1′-homocarbonucleosides bicyclo[2.2.1]heptane nucleosides 6-chloropurine 6-substituted adenine nucleosides antiviral activity herpesviruses molecular docking |
| url |
https://www.mdpi.com/1420-3049/24/13/2446 |
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