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

Yi-Wei Sun; Yan Ju; Cai-Hong Liu; Kai-Cheng Du; Da-Li Meng

doi:10.1016/j.bioorg.2019.103551

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

Bioorg Chem. 2020 Jan:95:103551. doi: 10.1016/j.bioorg.2019.103551. Epub 2019 Dec 28.

Authors

Yi-Wei Sun¹, Yan Ju¹, Cai-Hong Liu¹, Kai-Cheng Du¹, Da-Li Meng²

Affiliations

¹ School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
² School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address: mengdl@syphu.edu.cn.

PMID: 31911301
DOI: 10.1016/j.bioorg.2019.103551

Abstract

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 Lévl 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 μM. 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-кB, in silico study was conducted and the results were in complete agreement with the experimental data for cytotoxicity evaluation.

Keywords: Artemisia argyi; In silico; In vitro; NF-кB inhibitor; Terpenoids.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma / pathology*
Humans
NF-kappa B / antagonists & inhibitors*
Sesquiterpenes, Guaiane / pharmacology*
Spectrum Analysis / methods
Stomach Neoplasms / pathology*
Tumor Cells, Cultured

Substances

NF-kappa B
Sesquiterpenes, Guaiane