6-alkylsalicylic acid analogues inhibit in vitro ATPase activity of heat shock protein 90

Abstract

The molecular chaperone heat shock protein 90 (Hsp90) is responsible for maintaining the correct folding and stability of many signaling proteins. It is a promising target of cancer therapeutics and several other diseases, including neurodegenerative disease, nerve injuries, inflammation, and infection. In an effort to identify new Hsp90 inhibitors from natural sources using an in vitro ATPase inhibition assay, two 6-alkylsalicylic acid analogues, salaceyin A and B were identified from the culture extract of Streptomyces. Salaceyin A and B exhibited moderate ATPase inhibitory activities with IC(50) values of 68.3 and 65.2 μM, respectively. Binding of salaceyins to human Hsp90α was examined by competition binding experiments with ATP-Sepharose beads. However, the compounds exhibited no degradation activity of Hsp90 client proteins, Her2, c-Raf, or Akt.

Anti-Cancer Properties of Ginkgolic Acids in Human Nasopharyngeal Carcinoma CNE-2Z Cells via Inhibition of Heat Shock Protein 90

“…Hsp90 ATPase activity was measured using the malachite green assay, as described previously [41]. Briefly, 2 µM Hsp90 protein, 0.2 mM ATP, and samples were added to 96-well plates and incubated for 2.5 h at 37 • C. After incubation, 80 µL of malachite green-molybdate solution was added to each well, and the plate was shaken, followed by quenching with 34% sodium citrate.…”

Enzymatic Glycosylation of Nonbenzoquinone Geldanamycin Analogs via Bacillus UDP-Glycosyltransferase

“…We treated cells with compounds at various concentrations for 72 h. Cell viability was detected by the standard sulforhodamine B (SRB) procedures. Western blot analyses were performed as described previously (33).…”