Cystargolides, 20S Proteasome Inhibitors Isolated from <i>Kitasatospora cystarginea</i>
作者:Krista A. Gill、Fabrice Berrué、Jennifer C. Arens、Gavin Carr、Russell G. Kerr
DOI:10.1021/np501060k
日期:2015.4.24
Two novel beta-lactone-containing natural products, cystargolides A (1) and B (2), were isolated from the actinomycete Kitasatospora cystarginea. The production of these two natural products was highlighted using a methodology associating liquid chromatography-high-resolution mass spectrometry (LC-HRMS) analysis and the statistical analysis tool principal component analysis (PCA). Their structures were elucidated by interpretation of NMR experiments and tandem mass spectrometry. The absolute configurations of the amino acid residues were determined using Marfeys method, and the relative configurations of the beta-lactone substituents were determined on the basis of the vicinal (3)J(HH) coupling value. Due to the presence of the beta-lactone, 1 and 2 were evaluated for their ability to inhibit the human 20S proteasome. 1 and 2 both inhibited the 20S proteasome in vitro with IC50 values of 0.35 and 0.93 mu M, respectively.