title: Contribution of Cage-Shaped Structure of Physalins to Their Mode of Action in Inhibition of NF-κB Activation.
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.
authors.affiliation: Synthetic Organic Chemistry Laboratory, RIKEN , 2-1 Hirosawa, Wako, Saitama 351-0198, Japan ; RIKEN Center for Sustainable Resource Science , 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ozawa
authors.affiliation: Synthetic Organic Chemistry Laboratory, RIKEN , 2-1 Hirosawa, Wako, Saitama 351-0198, Japan ; Department of Chemistry, Graduate School of Science, Kyoto University , Sakyo, Kyoto 606-8502, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Morita
authors.affiliation: Synthetic Organic Chemistry Laboratory, RIKEN , 2-1 Hirosawa, Wako, Saitama 351-0198, Japan ; RIKEN Center for Sustainable Resource Science , 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Hirai
authors.affiliation: Synthetic Organic Chemistry Laboratory, RIKEN , 2-1 Hirosawa, Wako, Saitama 351-0198, Japan ; ERATO-JST , 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Tamura
authors.affiliation: Nagoya Institute of Technology , Gokiso-cho, Showa-ku, Nagoya, Aichi 466-8555, Japan ; Nakanoshima Science Laboratory, Osaka Science Museum , 4-2-1 Nakanoshima, Kita-ku, Osaka 530-0005, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Kawai
authors.affiliation: Synthetic Organic Chemistry Laboratory, RIKEN , 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Tsuchiya
authors.affiliation: Synthetic Organic Chemistry Laboratory, RIKEN , 2-1 Hirosawa, Wako, Saitama 351-0198, Japan ; RIKEN Center for Sustainable Resource Science , 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Oonuma
authors.affiliation: Department of Chemistry, Graduate School of Science, Kyoto University , Sakyo, Kyoto 606-8502, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Maruoka
authors.affiliation: Synthetic Organic Chemistry Laboratory, RIKEN , 2-1 Hirosawa, Wako, Saitama 351-0198, Japan ; RIKEN Center for Sustainable Resource Science , 2-1 Hirosawa, Wako, Saitama 351-0198, Japan ; ERATO-JST , 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Mikiko
authors.initials: M
authors.lastname: Sodeoka
keywords: NF-κB; Physalis plants; SAR; highly oxygenated steroid; physalin; synthetic analogues; withanolide