1. Phenoxazine nucleoside derivatives with a multiple activity against RNA and DNA viruses
- Author
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Andrey V. Aralov, Anna A. Shtro, Elena S. Matyugina, Graciela Andrei, Viktor P. Volok, Yulia V. Nikolaeva, Dmitry I. Osolodkin, Aydar Ishmukhametov, Vladimir A. Korshun, Liubov I. Kozlovskaya, Robert Snoeck, Artjom V. Jegorov, Evgeny S. Belyaev, and Alexey A. Chistov
- Subjects
RNA viruses ,Microbial Sensitivity Tests ,medicine.disease_cause ,Virus Replication ,01 natural sciences ,Antiviral Agents ,Article ,Madin Darby Canine Kidney Cells ,03 medical and health sciences ,chemistry.chemical_compound ,Structure-Activity Relationship ,Dogs ,Cell Line, Tumor ,Drug Discovery ,Chlorocebus aethiops ,Oxazines ,medicine ,Structure–activity relationship ,Animals ,Humans ,Phenoxazine ,Vero Cells ,030304 developmental biology ,Coronavirus ,Pharmacology ,0303 health sciences ,Nucleoside analogue ,Molecular Structure ,010405 organic chemistry ,Chemistry ,SARS-CoV-2 ,Organic Chemistry ,DNA Viruses ,RNA ,Nucleosides ,General Medicine ,Antivirals ,Virology ,0104 chemical sciences ,Viral replication ,Nucleoside analogs ,DNA viruses ,Nucleoside ,DNA ,medicine.drug - Abstract
Emerging and re-emerging viruses periodically cause outbreaks and epidemics all over the world, eventually leading to global events such as the current pandemic of the novel SARS-CoV-2 coronavirus infection COVID-19. Therefore, an urgent need for novel antivirals is crystal clear. Here we present the synthesis and evaluation of an antiviral activity of phenoxazine-based nucleoside analogs divided into three groups: (1) 8-alkoxy-substituted, (2) acyclic, and (3) carbocyclic. The antiviral activity was assessed against a structurally and phylogenetically diverse panel of RNA and DNA viruses from 25 species. Four compounds (11a-c, 12c) inhibited 4 DNA/RNA viruses with EC50 ≤ 20 μM. Toxicity of the compounds for the cell lines used for virus cultivation was negligible in most cases. In addition, previously reported and newly synthesized phenoxazine derivatives were evaluated against SARS-CoV-2, and some of them showed promising inhibition of reproduction with EC50 values in low micromolar range, although accompanied by commensurate cytotoxicity., Graphical abstract Image 1
- Published
- 2021