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 |
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Pages (from-to) | 730-735 |
Number of pages | 6 |
Journal | ACS Medicinal Chemistry Letters |
Volume | 4 |
Issue number | 8 |
DOIs | |
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