Anti-inflammatory drimane sesquiterpene lactones from an Aspergillus species

被引：16

作者：

Felix, Silke ^{[1
]}

Sandjo, Louis P. ^{[2
]}

Opatz, Till ^{[2
]}

Erkel, Gerhard ^{[3
]}

机构：

[1] Inst Biotechnol & Drug Res IBWF, D-67663 Kaiserslautern, Germany

[2] Johannes Gutenberg Univ Mainz, Inst Organ Chem, D-55128 Mainz, Germany

[3] Univ Kaiserslautern, Dept Mol Biotechnol & Syst Biol, D-67663 Kaiserslautern, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2014年 / 22卷 / 11期

关键词：

CXCL10; Inhibitor; Inflammation; Fungal metabolites; NF-KAPPA-B; AIRWAY SMOOTH-MUSCLE; IFN-GAMMA; TNF-ALPHA; CXCL10; CXCR3; EXPRESSION; CHEMOKINE; CELLS;

D O I：

10.1016/j.bmc.2014.04.015

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

IFN-gamma inducible protein 10 (IP-10, CXCL10) is a 10 kDa chemokine, which is secreted from various cell types after exposure to pro-inflammatory stimuli. This chemokine is a ligand for the CXCR3 receptor and regulates immune responses by activating and recruiting leukocytes such as T cells, eosinophils, monocytes, and NK cells to sites of inflammation. Altered expression of CXCL10 has been associated with chronic inflammatory and infectious diseases and therefore CXCL10 represents a promising target for the development of new anti-inflammatory drugs. In a search for inhibitors of CXCL10 promoter activity, three structurally related drimane sesquiterpene lactones (compounds 1-3) were isolated from fermentations of an Aspergillus species. Compounds 1 and 2 inhibited the IFN-gamma/TNF-alpha/IL-1 beta induced CXCL10 promoter activity in transiently transfected human DLD-1 colon carcinoma cells in a dose-dependent manner with IC50 values of 12.4 mu M for 1 and 55 mu M for 2, whereas 3 was devoid of any biological activity. Moreover, compounds 1 and 2 reduced CXCL10 mRNA levels and synthesis in IFN-gamma/TNF-alpha/IL-1 beta stimulated DLD-1 cells. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：2912 / 2918

页数：7

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