Structural Features Defining NF-κB Inhibition by Lignan-Inspired Benzofurans and Benzothiophenes.

Toan Dao-Huy,Simone Latkolik,Marko D Mihovilovic,Verena M Dirsch,Julia Bräuer,Andreas Pfeil,Hermann Stuppner,Michael Schnürch

doi:10.3390/biom10081131

Toan Dao-Huy, Simone Latkolik + Show 6 more

Open Access

https://doi.org/10.3390/biom10081131

Copy DOI

Abstract

A series of 2-arylbenzofurans and 2-arylbenzothiophenes was synthesized carrying three different side chains in position five. The synthesized compounds were tested for NF-κB inhibition to establish a structure activity relationship. It was found that both, the side chain in position five and the substitution pattern of the aryl moiety in position two have a significant influence on the inhibitory activity.

Highlights

Inflammation is a protective host response to infection or tissue damage [1,2]
It was found that both, the side chain in position five and the substitution pattern of the aryl moiety in position two have a significant influence on the inhibitory activity
Whereas an acute response resulting in the elimination of the noxious agent is beneficial, long lasting chronic inflammatory states contribute to the development of many pathologies like autoimmune, metabolic, cardiovascular and neurodegenerative diseases or cancer [2,3], PAMPs as well as DAMPs activate pattern recognition receptors (PRR) that transduce signals to NF-κB signaling pathways [2], which play a pivotal role in chronic and acute inflammation [4]

Summary

Introduction

Inflammation is a protective host response to infection or tissue damage (including stress or dyshomeostasis) [1,2]. Whereas an acute response resulting in the elimination of the noxious agent is beneficial, long lasting chronic inflammatory states contribute to the development of many pathologies like autoimmune, metabolic, cardiovascular and neurodegenerative diseases or cancer [2,3], PAMPs (pathogen-associated molecular patterns) as well as DAMPs (damage-associated molecular patterns) activate pattern recognition receptors (PRR) that transduce signals to NF-κB signaling pathways [2], which play a pivotal role in chronic and acute inflammation [4]. The extract of the Rhatany root was introduced into European medicine over 200 years ago as a remedy against stomach aches, diarrhea, menstrual problems, nose bleeds and oropharyngeal inflammation [5,6]. In a study on constituents of the Rhatany root, the group of Stuppner isolated eleven lignans from the dichloromethane extract of the root (Figure 1) [7]

Methods

Results

Conclusion