Contribution of cage-shaped structure of physalins to their mode of action in inhibition of NF-κB activation

Masaaki Ozawa, Masaki Morita, Go Hirai, Satoru Tamura, Masao Kawai, Ayako Tsuchiya, Kana Oonuma, Keiji Maruoka, Mikiko Sodeoka

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

A library of oxygenated natural steroids, including physalins, withanolides, and perulactones, coupled with the synthetic cage-shaped right-side structure of type B physalins, was constructed. SAR studies for inhibition of NF-κB activation showed the importance of both the B-ring and the oxygenated right-side partial structure. The 5β,6β-epoxy derivatives of both physalins and withanolides showed similar profiles of inhibition of NF-κB activation and appeared to act on NF-κB signaling via inhibition of phosphorylation and degradation of IκBα. In contrast, type B physalins with C5-C6 olefin functionality inhibited nuclear translocation and DNA binding of RelA/p50 protein dimer, which lie downstream of IκBα degradation, although withanolides having the same AB-ring functionality did not. These results indicated that the right-side partial structure of these steroids influences their mode of action.

Original languageEnglish
Pages (from-to)730-735
Number of pages6
JournalACS Medicinal Chemistry Letters
Volume4
Issue number8
DOIs
Publication statusPublished - 2013 Aug 8

Keywords

  • NF-κB
  • Physalis plants
  • SAR
  • highly oxygenated steroid
  • physalin
  • synthetic analogues
  • withanolide

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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    Ozawa, M., Morita, M., Hirai, G., Tamura, S., Kawai, M., Tsuchiya, A., Oonuma, K., Maruoka, K., & Sodeoka, M. (2013). Contribution of cage-shaped structure of physalins to their mode of action in inhibition of NF-κB activation. ACS Medicinal Chemistry Letters, 4(8), 730-735. https://doi.org/10.1021/ml400144e