3′-fluorine-substitution in 3′-fluorocarbocyclic oxetanocin A augments the drug's inhibition of HHV-6B propagation in chronically infected cultures

Ping Wang, Kenji Abe, Tomoko Ojima, Junko H. Ohyashiki, Hitoshi Satoh, Tokumi Maruyama, Hiroshi Nagata, Hiroshi Tanaka, Kohtaro Yamamoto

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

An infection of TaY cells, which originated from an adult T-cell leukemia, with an HHV-6B OK isolate resulted in a chronically infected culture, termed TaY(OK). Cell cloning analysis revealed that the TaY(OK) culture consisted of a mixture of cells permissive and refractory to the infection, and that the permissive cells were continuously produced from the refractory cell population. Since the chronically infected culture has been maintained for over 2 years without the addition of uninfected Tay cells, we used it for an evaluation of the antiviral potency of nucleoside analogs, especially carbocyclic oxetanocins (C.OXTs). MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assays showed a lack of toxicity of ganciclovir (GCV), C.OXTs, and their derivatives, to TaY(OK) cells at 1 μM. Therefore we compared the antiviral potencies of these drugs at 1 μM by monitoring the viral loads produced during a 1-day period during the course of the drug treatment. Among the drugs tested, 3′-fluorocarbocyclic oxetanocin A (3′FC.OXT-A) was the most effective for inhibiting the virus production, and at concentrations ranging from 0.5 μM to 10 μM, the inhibition of the viral production was dose-dependent. A comparison of the chemical structures of the derivatives with that of C.OXT-A, which is the parental molecule, suggested that the 3′-fluorine-modification might account for the higher anti-HHV-6 activity and lower cytotoxicity.

Original languageEnglish
Pages (from-to)457-466
Number of pages10
JournalMICROBIOLOGY and IMMUNOLOGY
Volume45
Issue number6
DOIs
Publication statusPublished - 2001

Keywords

  • 3′-Fluorocarbocyclic oxetanocin A
  • Chronic infection
  • HHV-6B

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

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