Synthesis and biological effect of chrom-4-one derivatives as functional inhibitors of heat shock protein 27

Soo Yeon Hwang, Soo Yeon Kwak, Youngjoo Kwon, Yun Sil Lee, Younghwa Na

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Heat Shock Protein 27 (HSP27) is a member of small heat shock proteins with a highly-conserved α-crystalline domain. It inhibits aggregation of damaged proteins through a complex structural systems of phosphorylation-dependent oligomerization and self-assembly. It has been demonstrated that HSP27 is involved in a variety of pathophysiological pathways with negative or positive protective activities. In this study, we synthesized six chromone analogs possessing thiiran-2-ylmethoxy or oxyran-2-ylmethoxy substituents and evaluated their biological activities against HSP27 protein. Compounds YK598-2, J4 and J2 induced significant abnormal HSP27 dimer formation in NCI-H460, a human lung cancer cell line. In synergistic anticancer activity test, the compounds effectively producing abnormal HSP27 cross-linking remarkably enhanced the antiproliferative activity of 17-AAG, a HSP90 inhibitor. Target specificity test using the HSP27-silenced cells (shHSP27) showed that compounds YK598-2, J4, and J2 significantly lost their cross-linking activity only under conditions when HSP27 was deprived of. In the evaluation of cancer cell sensitization with cisplatin, cisplatin-induced lung cancer cell growth inhibition was sensitized with statistical significance by J4 and J2 as compared to compound alone treatment. These results suggest that abnormal HSP27 dimerization can be an efficient control point for cancer cell proliferation and chromone compounds might have potential as anticancer agents that modulate abnormal HSP27 dimerization.

Original languageEnglish
Pages (from-to)892-900
Number of pages9
JournalEuropean Journal of Medicinal Chemistry
StatePublished - 2017

Bibliographical note

Funding Information:
This work was supported by grants from the Nuclear R&D Program ( 2015M2A2A7A 03044831 ) and the Bio & Medical Technology Development Program ( NRF2014M3A9A9073 908 ) of the National Research Foundation of Korea (NRF), funded by the Korean government (Ministry of Science, ICT & Future Planning) .

Publisher Copyright:
© 2017 Elsevier Masson SAS


  • Anti-cancer activity
  • Chromone analogue
  • HSP-27 dimerization


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