Project

Investigation of anti-inflammatory and cytotoxic guaianolide lactones: isolation and characterisation of naturally occuring NF-B inhibitors from Laserpitium L. species and their structural modification in order to enhance their activity

Duration
01 October 2014 → 30 November 2015
Funding
Regional and community funding: Special Research Fund, Research Foundation - Flanders (FWO)
Research disciplines
  • Natural sciences
    • Systems biology
Keywords
autoinflammatoire
 
Project description

The aim of this project is an investigation of the mechanism by which guaianolide
lactones exert NF-kappaB and/or AP-1 inhibition in a strong, concentration
dependent manner, and to explain their activity as potential anti-inflammatory and
cytotoxic agents.
Sesquiterpene lactones are plant metabolites of a complex structure, with a limited
distribution and numerous pharmacological activities, so they are gaining scientific
interest and clinical applications. Species of the genus Laserpitium (Apiaceae) are
shown to be rich in these compounds, particularly guaianolides. In our previous
investigation, fourteen lactones were isolated, five of them being novel highly
esterified guaianolides. Some of the compounds exerted a strong and reproducible
inhibition of the activity of NF-kappaB in a series of first screening tests, and
cytotoxic activity in human breast adenocarcinoma cell lines.
Our goal is also to further investigate minor components of complex extracts of four
selected Laserpitium species in order to identify novel natural NF-kappaB
inhibitors.
Furthermore, using chemical modification and semisynthetic transformations of
functional groups and side chains in isolated molecules of interest, „chemical
space“ will be investigated, determining the structural features that contribute to the
above mentioned activities. By establishing the structure activity relationship of
isolated and modified molecules, our goal is to obtain candidates for clinical
application.