Synthesis and biological evaluation of pharbinilic acid and derivatives as NF-κB pathway inhibitors

J R Annand; P A Bruno; A K Mapp; C S Schindler

doi:10.1039/c5cc02918j

Synthesis and biological evaluation of pharbinilic acid and derivatives as NF-κB pathway inhibitors

Chem Commun (Camb). 2015 May 28;51(43):8990-3. doi: 10.1039/c5cc02918j.

Authors

J R Annand¹, P A Bruno, A K Mapp, C S Schindler

Affiliation

¹ Department of Chemistry, University of Michigan, 930 North University Ave., Ann Arbor, MI 48109, USA. [email protected].

PMID: 25932702
DOI: 10.1039/c5cc02918j

Abstract

A 7-step synthesis of pharbinilic acid, a member of the gibberellin family of natural products and the first naturally occurring allogibberic acid, is reported. An efficient decarboxylative aromatization reaction enables the synthesis of pharbinilic acid and related analogs for evaluation as modulators of NF-κB activity. Remarkably, one analog displays a 2 μM IC50 in an NF-κB activity assay and inhibits an endogenous NF-κB-regulated pathway.

MeSH terms

Biological Products / chemical synthesis
Biological Products / chemistry
Biological Products / metabolism
Catalysis
Cell Line, Tumor
Gene Expression / drug effects
HeLa Cells
Heterocyclic Compounds, 4 or More Rings / chemical synthesis
Heterocyclic Compounds, 4 or More Rings / chemistry*
Heterocyclic Compounds, 4 or More Rings / pharmacology
Humans
Interleukin-1beta / pharmacology
NF-kappa B / antagonists & inhibitors*
NF-kappa B / genetics
NF-kappa B / metabolism
Palladium / chemistry
Protein Binding
Signal Transduction / drug effects

Substances

Biological Products
Heterocyclic Compounds, 4 or More Rings
Interleukin-1beta
NF-kappa B
pharbinilic acid
Palladium