Abstract
Herbal extracts containing sesquiterpene lactones have been extensively used in traditional medicine and are known to be rich in α,β-unsaturated functionalities that can covalently engage target proteins. Here we report synthetic methodologies to access analogues of deoxyelephantopin, a sesquiterpene lactone with anticancer properties. Using alkyne-tagged cellular probes and quantitative proteomics analysis, we identified several cellular targets of deoxyelephantopin. We further demonstrate that deoxyelephantopin antagonizes PPARγ activity in situ via covalent engagement of a cysteine residue in the zinc-finger motif of this nuclear receptor.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antineoplastic Agents / chemical synthesis
-
Antineoplastic Agents / pharmacology*
-
Antineoplastic Agents / therapeutic use
-
Apoptosis / drug effects*
-
Cell Line, Tumor
-
Cell Proliferation / drug effects*
-
Cysteine / metabolism
-
Humans
-
Lactones / analysis
-
Lactones / chemical synthesis
-
Lactones / pharmacology*
-
Lactones / therapeutic use
-
Molecular Targeted Therapy / methods
-
Neoplasms / drug therapy
-
PPAR gamma / antagonists & inhibitors*
-
PPAR gamma / metabolism
-
Proteomics / methods
-
Recombinant Proteins / metabolism
-
Sesquiterpenes / analysis
-
Sesquiterpenes / chemical synthesis
-
Sesquiterpenes / pharmacology*
-
Sesquiterpenes / therapeutic use
-
Zinc Fingers / drug effects
Substances
-
Antineoplastic Agents
-
Lactones
-
PPAR gamma
-
Recombinant Proteins
-
Sesquiterpenes
-
deoxyelephantopin
-
Cysteine