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

doi:10.1021/ml400144e

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

SCI - Chemistry

Research output: Contribution to journal › Article › peer-review

16 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 language	English
Pages (from-to)	730-735
Number of pages	6
Journal	ACS Medicinal Chemistry Letters
Volume	4
Issue number	8
DOIs	https://doi.org/10.1021/ml400144e
Publication status	Published - 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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Contribution of cage-shaped structure of physalins to their mode of action in inhibition of NF-κB activation. / Ozawa, Masaaki; Morita, Masaki; Hirai, Go; Tamura, Satoru; Kawai, Masao; Tsuchiya, Ayako; Oonuma, Kana; Maruoka, Keiji; Sodeoka, Mikiko.

In: ACS Medicinal Chemistry Letters, Vol. 4, No. 8, 08.08.2013, p. 730-735.

Research output: Contribution to journal › Article › peer-review

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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.",

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AU - Kawai, Masao

AU - Tsuchiya, Ayako

AU - Oonuma, Kana

AU - Maruoka, Keiji

AU - Sodeoka, Mikiko

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AB - 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.

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

Abstract

Keywords

ASJC Scopus subject areas

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