A Chemical–Biological
Study Reveals C<sub>9</sub>‑type Iridoids as Novel Heat Shock
Protein 90 (Hsp90) Inhibitors
- Publication date
- Publisher
Abstract
The potential of heat shock protein 90 (Hsp90) as a therapeutic
target for numerous diseases has made the identification and optimization
of novel Hsp90 inhibitors an emerging therapeutic strategy. A surface
plasmon resonance (SPR) approach was adopted to screen some iridoids
for their Hsp90 α binding capability. Twenty-four iridoid derivatives,
including 13 new natural compounds, were isolated from the leaves
of <i>Tabebuia argentea</i> and petioles of <i>Catalpa
bignonioides</i>. Their structures were elucidated by NMR, electrospray
ionization mass spectrometry, and chemical methods. By means of a
panel of chemical and biological approaches, four iridoids were demonstrated
to bind Hsp90 α. In particular, the dimeric iridoid argenteoside
A was shown to efficiently inhibit the chaperone in biochemical and
cellular assays. Our results disclose C<sub>9</sub>-type iridoids
as a novel class of Hsp90 inhibitors
