Phenoxazine nucleoside derivatives with a multiple activity against RNA and DNA viruses.

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 EC 50 ≤ 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 EC 50 values in low micromolar range, although accompanied by commensurate cytotoxicity. [Display omitted] • 8-Alkoxy-substituted, acyclic and carbocyclic phenoxazine derivatives were synthesized. • The activity was assessed against a broad panel of RNA/DNA viruses from 25 species. • Four compounds (11a-c , 12c) inhibited 4 DNA/RNA viruses with EC 50 ≤ 20 μM. • Three of them exhibited submicromolar activity against VZV. • The compounds did not show pronounced cytotoxicity against all the studied cell lines. [ABSTRACT FROM AUTHOR]