Antiviral activity spectrum of phenoxazine nucleoside derivatives
Kozlovskaya L. I., Andrei G., Orlov A. A., Khvatov E. V., Koruchekov A. A., Belyaev E. S., Nikolaev E. N., Korshun V. A., Snoeck R., Osolodkin D. I., Matyugina E. S., Aralov A. V.
Antiviral Research
Vol.163, P. 117-124
Опубликовано: 2019
Тип ресурса: Статья
DOI:10.1016/j.antiviral.2019.01.010
Аннотация:
The phenoxazine scaffold is widely used to stabilize nucleic acid duplexes, as a part of fluorescent probes for the study of nucleic acid structure, recognition, and metabolism, etc. Here we present the synthesis of phenoxazine-based nucleoside derivatives and their antiviral activity against a panel of structurally diverse viruses: enveloped DNA herpesviruses varicella zoster virus (VZV) and human cytomegalovirus, enveloped RNA tick-borne encephalitis virus (TBEV), and non-enveloped RNA enteroviruses. Studied compounds were effective against DNA and RNA viruses reproduction in cell culture. 3-(2′-Deoxy-β-D-ribofuranosyl)-1,3-diaza-2-oxophenoxazine proved to be a potent inhibitor of VZV replication with superior activity against wild type than thymidine kinase deficient strains (EC 50 0.06 and 10 μM, respectively). This compound did not show cytotoxicity on all the studied cell lines. Several compounds showed promising activity against TBEV (EC 50 0.35–0.91 μM), but the activity was ac
Ключевые слова:
3 (2' deoxy beta dextro ribofuranosyl) 1,3 diaza 2 oxophenoxazine; 5 (2 bromovinyl) 2' deoxyuridine; aciclovir; antivirus agent; cidofovir; fluorescent dye; ganciclovir; nucleic acid; nucleoside derivative; phenoxazine derivative; thymidine kinase; unclassified drug; virus RNA; antivirus agent; DNA virus; nucleoside; oxazine derivative; phenoxazine; animal cell; antiviral activity; Article; CC50; cell growth; cell structure; controlled study; drug cytotoxicity; drug potency; EC50; Enterovirus; human; human cell; Human cytomegalovirus; Human respiratory syncytial virus; nonhuman; nucleic acid structure; priority journal; Punta Toro virus; Sindbis virus; Tick borne encephalitis virus; Varicella zoster virus; Vesiculovirus; virus inhibition; virus replication; cell line; chemical structure; chemistry; drug effect; physiology; RNA virus; Antiviral Agents; Cell Line; DNA Viruses; Humans; Molecular Structure; Nucleosides; Oxazines; RNA Viruses; Virus Replication
Язык текста: Английский
ISSN: 1872-9096
Kozlovskaya L. I. Lyubov` Igorevna 1984-
Andrei G.
Orlov A. A. Anton Anatolyevich 1991-
Khvatov E. V.
Koruchekov A. A.
Belyaev E. S.
Nikolaev E. N.
Korshun V. A.
Snoeck R.
Osolodkin D. I. Dmitrij Ivanovich 1985-
Matyugina E. S.
Aralov A. V.
Козловская Л. И. Любовь Игоревна 1984-
Андреи Г.
Орлов А. А. Антон Анатольевич 1991-
Хватов Е. В.
Коручеков А. А.
Беляев Е. С.
Николаев Е. Н.
Коршун В. А.
Сноеcк Р.
Осолодкин Д. И. Дмитрий Иванович 1985-
Матюгина Е. С.
Аралов А. В.
Antiviral activity spectrum of phenoxazine nucleoside derivatives
Текст визуальный непосредственный
Antiviral Research
Elsevier Science Publisher B.V.
Vol.163 P. 117-124
2019
Статья
3 (2' deoxy beta dextro ribofuranosyl) 1,3 diaza 2 oxophenoxazine 5 (2 bromovinyl) 2' deoxyuridine aciclovir antivirus agent cidofovir fluorescent dye ganciclovir nucleic acid nucleoside derivative phenoxazine derivative thymidine kinase unclassified drug virus RNA antivirus agent DNA virus nucleoside oxazine derivative phenoxazine animal cell antiviral activity Article CC50 cell growth cell structure controlled study drug cytotoxicity drug potency EC50 Enterovirus human human cell Human cytomegalovirus Human respiratory syncytial virus nonhuman nucleic acid structure priority journal Punta Toro virus Sindbis virus Tick borne encephalitis virus Varicella zoster virus Vesiculovirus virus inhibition virus replication cell line chemical structure chemistry drug effect physiology RNA virus Antiviral Agents Cell Line DNA Viruses Humans Molecular Structure Nucleosides Oxazines RNA Viruses Virus Replication
The phenoxazine scaffold is widely used to stabilize nucleic acid duplexes, as a part of fluorescent probes for the study of nucleic acid structure, recognition, and metabolism, etc. Here we present the synthesis of phenoxazine-based nucleoside derivatives and their antiviral activity against a panel of structurally diverse viruses: enveloped DNA herpesviruses varicella zoster virus (VZV) and human cytomegalovirus, enveloped RNA tick-borne encephalitis virus (TBEV), and non-enveloped RNA enteroviruses. Studied compounds were effective against DNA and RNA viruses reproduction in cell culture. 3-(2′-Deoxy-β-D-ribofuranosyl)-1,3-diaza-2-oxophenoxazine proved to be a potent inhibitor of VZV replication with superior activity against wild type than thymidine kinase deficient strains (EC 50 0.06 and 10 μM, respectively). This compound did not show cytotoxicity on all the studied cell lines. Several compounds showed promising activity against TBEV (EC 50 0.35–0.91 μM), but the activity was ac