Enzymatic synthesis of novel purine nucleosides bearing a chiral benzoxazine fragment
| Autor: | Roman S. Esipov, Tatyana I. Muravyova, Alexander S. Paramonov, Inessa S. Muzyka, Galina L. Levit, Irina D. Konstantinova, Barbara Z. Eletskaya, Valeria L. Andronova, Alexei L. Kayushin, Valery N. Charushin, Victor P. Krasnov, M. A. Kostromina, Anatoly I. Miroshnikov, Galegov Ga, Dmitry A. Gruzdev |
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| Rok vydání: | 2018 |
| Předmět: |
Purine
Deoxyribonucleosides Stereochemistry Adenosine Deaminase Cell Survival Deamination Herpesvirus 1 Human medicine.disease_cause 01 natural sciences Biochemistry Antiviral Agents Nucleobase chemistry.chemical_compound Adenosine deaminase Drug Discovery Chlorocebus aethiops Drug Resistance Viral medicine Escherichia coli Animals Humans Vero Cells Pharmacology chemistry.chemical_classification biology 010405 organic chemistry Escherichia coli Proteins Organic Chemistry Stereoisomerism Purine Nucleosides 0104 chemical sciences Benzoxazines 010404 medicinal & biomolecular chemistry Enzyme chemistry biology.protein Molecular Medicine Nucleoside |
| Zdroj: | Chemical biologydrug design. 93(4) |
| ISSN: | 1747-0285 |
| Popis: | A series of ribo- and deoxyribonucleosides bearing 2-aminopurine as a nucleobase with 7,8-difluoro- 3,4-dihydro-3-methyl-2H-[1,4]benzoxazine (conjugated directly or through an aminohexanoyl spacer) was synthesized using an enzymatic transglycosylation reaction. Nucleosides 3-6 were resistant to deamination under action of adenosine deaminase (ADA) Escherichia coli and ADA from calf intestine. The antiviral activity of the modified nucleosides was evaluated against herpes simplex virus type 1 (HSV-1, strain L2). It has been shown that at sub-toxic concentrations, nucleoside (S)-4-[2-amino-9-(β-D-ribofuranosyl)-purin-6-yl]-7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine exhibit significant antiviral activity (SI > 32) on the model of HSV-1 in vitro, including an acyclovir-resistant virus strain (HSV-1, strain L2/R). |
| Databáze: | OpenAIRE |
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