Synthesis and in vitro anti-HSV-1 activity of a novel Hsp90 inhibitor BJ-B11

Bioorg Med Chem Lett. 2011 Mar 15;21(6):1675-7. doi: 10.1016/j.bmcl.2011.01.098. Epub 2011 Jan 27.

Abstract

In this study, a novel Hsp90 inhibitor BJ-B11, was synthesized and evaluated for in vitro antiviral activity against several viruses. Possible anti-HSV-1 mechanisms were also investigated. BJ-B11 displayed no antiviral activity against coxsackievirus B(3) (CVB(3)), human respiratory syncytial virus (RSV) and influenza virus (H1N1), but exhibited potent anti-HSV-1 and HSV-2 activity with EC(50) values of 0.42±0.18 μM and 0.60±0.21 μM, respectively. Additionally, the inhibitory effects of BJ-B11 against HSV-1 were likely to be introduced at early stage of infection. Our results indicate that BJ-B11 with alternative mechanisms of action is potent as an anti-HSV clinical trial candidate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacology*
  • Benzamides / chemical synthesis*
  • Benzamides / pharmacology*
  • HSP90 Heat-Shock Proteins / chemical synthesis*
  • HSP90 Heat-Shock Proteins / pharmacology*
  • Herpesvirus 1, Human / drug effects*
  • Herpesvirus 1, Human / genetics
  • Indazoles / chemical synthesis*
  • Indazoles / pharmacology*
  • Microbial Sensitivity Tests
  • Polymerase Chain Reaction

Substances

  • 2-(4-acetyloxycyclohexylamino)-4-(3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indazol-1-yl)-benzamide
  • Antiviral Agents
  • Benzamides
  • HSP90 Heat-Shock Proteins
  • Indazoles