(+)-Camphor and (-)-borneol derivatives as potential anti-orthopoxvirus agents

Arch Pharm (Weinheim). 2021 Jun;354(6):e2100038. doi: 10.1002/ardp.202100038. Epub 2021 Feb 19.

Abstract

Although the World Health Organisation had announced that smallpox was eradicated over 40 years ago, the disease and other related pathogenic poxviruses such as monkeypox remain potential bioterrorist weapons and could also re-emerge as natural infections. We have previously reported (+)-camphor and (-)-borneol derivatives with an antiviral activity against the vaccinia virus. This virus is similar to the variola virus (VARV), the causative agent of smallpox, but can be studied at BSL-2 facilities. In the present study, we evaluated the antiviral activity of the most potent compounds against VARV, cowpox virus, and ectromelia virus (ECTV). Among the compounds tested, 4-bromo-N'-((1R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene)benzohydrazide 18 is the most effective compound against various orthopoxviruses, including VARV, with an EC50 value of 13.9 μM and a selectivity index of 206. Also, (+)-camphor thiosemicarbazone 9 was found to be active against VARV and ECTV.

Keywords: (+)-camphor; (−)-borneol; cowpox virus; ectromelia virus; vaccinia virus; variola virus.

MeSH terms

  • Animals
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Camphanes* / chemical synthesis
  • Camphanes* / chemistry
  • Camphanes* / pharmacology
  • Camphor* / analogs & derivatives
  • Camphor* / chemistry
  • Camphor* / pharmacology
  • Cells, Cultured
  • Humans
  • Isoindoles* / chemical synthesis
  • Isoindoles* / chemistry
  • Isoindoles* / pharmacology
  • Orthopoxvirus / classification
  • Orthopoxvirus / drug effects*
  • Orthopoxvirus / pathogenicity
  • Orthopoxvirus / physiology
  • Poxviridae Infections / drug therapy
  • Poxviridae Infections / virology
  • Thiosemicarbazones / chemistry
  • Thiosemicarbazones / pharmacology

Substances

  • Antiviral Agents
  • Camphanes
  • Isoindoles
  • Thiosemicarbazones
  • Camphor
  • isoborneol