Contribution of Cage-Shaped Structure of Physalins to Their Mode of Action in Inhibition of NF-κB Activation.
Basic Information
ID: ALA2406967
Journal: ACS Med Chem Lett
Title: Contribution of Cage-Shaped Structure of Physalins to Their Mode of Action in Inhibition of NF-κB Activation.
Authors: Ozawa M, Morita M, Hirai G, Tamura S, Kawai M, Tsuchiya A, Oonuma K, Maruoka K, Sodeoka M.
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.
CiteXplore: 24900739
DOI: 10.1021/ml400144e
Patent ID: ┄