Withapubesides A-D: natural inducible nitric oxide synthase (iNOS) inhibitors from Physalis pubescens

Abstract

Four new steroid glycosides, withapubesides A-D (1-4), were isolated from the stems of Physalis pubescens L. Their structures were elucidated primarily by NMR experiments. The absolute configurations of 1 and 2 were deduced by single-crystal X-ray diffraction and ECD data analysis, respectively. Compound 3 has shown significant inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages with an IC₅₀ value of 12.8 μM and moderate cytostatic activity against human carcinoma cells (786-O, C4-2B, 22Rvl, A375 and A375S2) with IC₅₀ values in the range of 3.05-9.47 μM. Molecular docking simulation demonstrated that 3 is bound in the inducible nitric oxide synthase (iNOS) active site heme pocket very well, which suggests that 3 might be a candidate for the development of iNOS inhibitors.