Polyhydroxyl guaianolide terpenoids as potential NF-κB inhibitors induced cytotoxicity in human gastric adenocarcinoma cell line

Six new guaiane-type sesquiterpenes (1-6), and one monoterpenoid (7) along with five known analogues (8-12), were isolated from the leaves of Artemisia argyi Levl et Vant. The new compounds were characterized by the basic analysis of the spectroscopic data (HRMS, 1D and 2D NMR), and the absolute configurations were determined by both calculated electronic circular dichroism and DP4 calculations. The inhibitory effects of 1-12 against human gastric adenocarcinoma (AGS) cells were investigated in vitro, among which 1-3 and 8 showed remarkable cytotoxic activity with IC50 values in the range of 6.69-10.25 mu M. The results suggested that the variation in the inhibitory activities of the compounds are the result of different substitutions on C-8. In order to rationalize the binding interactions of active compounds with the active site of NF-kappa B, in silico study was conducted and the results were in complete agreement with the experimental data for cytotoxicity evaluation.