Synthesis and anti-Hantaan virus activity of N1-3-fluorophenyl-inosine

Dong Hoon Chung, J. Jacob Strouse, Yanjie Sun, Jeffrey B. Arterburn, William B. Parker, Colleen Jonsson

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

As part of an ongoing effort to develop new antiviral nucleoside analogs, our interest was drawn to N1-aryl purines as a novel structural class and potential scaffold for drug discovery. Herein, we describe the synthesis of N1-3-fluorophenyl-inosine (FPI) and N1-3-fluorophenyl-hypoxanthine (FP-Hx) and their antiviral activity against hantaviruses. The EC50 for FPI and FP-Hx were 94 and 234 μM, respectively, against Hantaan virus. FPI was not toxic to mammalian cells at concentrations that exhibited antiviral activity. Analysis of its metabolism revealed a low conversion of FPI in Vero E6 or human cells to a 5′-triphosphate, and it was a poor substrate for human purine nucleoside phosphorylase. Further, the compound did not alter GTP levels indicating FPI does not inhibit inosine monophosphate dehydrogenase. With respect to the virus, FPI did not decrease viral RNA levels or increase the mutation frequency of the viral RNA. This suggests that the antiviral activity of FPI might be solely due to the interaction of FPI or its metabolites with viral or host proteins involved in post-replication events that would affect the levels of infectious virus released. Synthesis of other compounds structurally similar to FPI is warranted to identify more potent agents that selectively abrogate production of infectious virus.

Original languageEnglish (US)
Pages (from-to)80-85
Number of pages6
JournalAntiviral Research
Volume83
Issue number1
DOIs
StatePublished - Jul 1 2009

Fingerprint

Hantaan virus
Inosine
Antiviral Agents
Viral RNA
Viruses
Purine-Nucleoside Phosphorylase
Hantavirus
Inosine Monophosphate
Purines
Hypoxanthine
N1-3-fluorophenyl-inosine
Poisons
Mutation Rate
Drug Discovery
Guanosine Triphosphate
Nucleosides
Oxidoreductases

All Science Journal Classification (ASJC) codes

  • Virology
  • Pharmacology

Cite this

Synthesis and anti-Hantaan virus activity of N1-3-fluorophenyl-inosine. / Chung, Dong Hoon; Strouse, J. Jacob; Sun, Yanjie; Arterburn, Jeffrey B.; Parker, William B.; Jonsson, Colleen.

In: Antiviral Research, Vol. 83, No. 1, 01.07.2009, p. 80-85.

Research output: Contribution to journalArticle

Chung, Dong Hoon ; Strouse, J. Jacob ; Sun, Yanjie ; Arterburn, Jeffrey B. ; Parker, William B. ; Jonsson, Colleen. / Synthesis and anti-Hantaan virus activity of N1-3-fluorophenyl-inosine. In: Antiviral Research. 2009 ; Vol. 83, No. 1. pp. 80-85.
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