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.

• Authors: Cheng-Zhu Wu, An Na Moon, Oksik Choi, Sun-Young Kang, Jung Joon Lee, Dongho Lee, Bang Yeon Hwang, Young Ho Kim, Hong-Sub Lee, Young-Soo Hong
• Journal: Archives of pharmacal research (Arch Pharm Res) Vol. 33 Issue 12 Pg. 1997-2001 (Dec 2010) ISSN: 1976-3786 [Electronic] Korea (South)
• PMID: 21191765 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP-sepharose
• Antineoplastic Agents
• HSP90 Heat-Shock Proteins
• Molecular Chaperones
• Salicylates
• salaceyin A
• salaceyin B
• Adenosine Triphosphate
• Sepharose
• ERBB2 protein, human
• Receptor, ErbB-2
• Proto-Oncogene Proteins c-akt
• Proto-Oncogene Proteins c-raf
• Adenosine Triphosphatases

Topics

• Adenosine Triphosphatases (antagonists & inhibitors, metabolism)
• Adenosine Triphosphate (metabolism)
• Antineoplastic Agents (metabolism, pharmacology)
• Binding, Competitive
• Cell Line, Tumor
• Female
• HSP90 Heat-Shock Proteins (antagonists & inhibitors, chemistry, metabolism)
• Humans
• Molecular Chaperones (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Proto-Oncogene Proteins c-raf (metabolism)
• Receptor, ErbB-2 (metabolism)
• Salicylates (isolation & purification, metabolism, pharmacology)
• Sepharose (analogs & derivatives, metabolism)
• Streptomyces (chemistry)