Skip to Content
MilliporeSigma
  • Enhancing the anti-inflammatory activity of chalcones by tuning the Michael acceptor site.

Enhancing the anti-inflammatory activity of chalcones by tuning the Michael acceptor site.

Organic & biomolecular chemistry (2015-01-27)
Hannelore Rücker, Nafisah Al-Rifai, Anne Rascle, Eva Gottfried, Lidia Brodziak-Jarosz, Clarissa Gerhäuser, Tobias P Dick, Sabine Amslinger
ABSTRACT

Inflammatory signaling pathways orchestrate the cellular response to infection and injury. These pathways are known to be modulated by compounds that alkylate cysteinyl thiols. One class of phytochemicals with strong thiol alkylating activity is the chalcones. In this study we tested fourteen chalcone derivatives, α-X-substituted 2',3,4,4'-tetramethoxychalcones (α-X-TMCs, X = H, F, Cl, Br, I, CN, Me, p-NO2-C6H4, Ph, p-OMe-C6H4, NO2, CF3, COOEt, COOH), for their ability to modulate inflammatory responses, as monitored by their influence on heme oxygenase-1 (HO-1) activity, inducible nitric oxide synthase (iNOS) activity, and cytokine expression levels. We confirmed that the transcriptional activity of Nrf2 was activated by α-X-TMCs while for NF-κB it was inhibited. For most α-X-TMCs, anti-inflammatory activity was positively correlated with thiol alkylating activity, i.e. stronger electrophiles (X = CF3, Br and Cl) being more potent. Notably, this correlation did not hold true for the strongest electrophiles (X = CN and NO2) which were found to be ineffective as anti-inflammatory compounds. These results emphasize the idea that chemical fine-tuning of electrophilicity is needed to achieve and optimize desired therapeutic effects.

MATERIALS
Product Number
Brand
Product Description

USP
Curcumin, United States Pharmacopeia (USP) Reference Standard
Supelco
Curcumin, matrix substance for MALDI-MS, ≥99.5% (HPLC)
Sigma-Aldrich
Ethyl acetate
Sigma-Aldrich
Ethyl acetate
Sigma-Aldrich
Dimethyl sulfoxide, Vetec, reagent grade, 99%
USP
Dimethyl sulfoxide, United States Pharmacopeia (USP) Reference Standard
Curcumin, primary reference standard
Sigma-Aldrich
Hexane, anhydrous, 95%
Sigma-Aldrich
Curcumin, from Curcuma longa (Turmeric), powder
Sigma-Aldrich
Curcumin, ≥94% (curcuminoid content), ≥80% (Curcumin)
Sigma-Aldrich
Sucrose, ≥99.5% (GC)
Sigma-Aldrich
Ethylenediaminetetraacetic acid solution, 0.02% in DPBS (0.5 mM), sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
Bilirubin, ≥98% (EmM/453 = 60), powder
Sigma-Aldrich
Sucrose, meets USP testing specifications
Sigma-Aldrich
8-Octanoyloxypyrene-1,3,6-trisulfonic acid trisodium salt, suitable for fluorescence, ≥90% (HPCE)
Sigma-Aldrich
Ethyl acetate, anhydrous, 99.8%
Sigma-Aldrich
Dimethyl sulfoxide, SAJ first grade, ≥99.0%
Sigma-Aldrich
Dimethyl sulfoxide, ≥99.0%, suitable for absorption spectrum analysis
Sigma-Aldrich
Hexane, HPLC Plus, for HPLC, GC, and residue analysis, ≥95%
Sigma-Aldrich
Dimethyl sulfoxide, suitable for HPLC
Sigma-Aldrich
Glycerol, JIS special grade, ≥99.0%
Sigma-Aldrich
Glycerol, SAJ first grade, ≥98.0%
Sigma-Aldrich
Dimethyl sulfoxide solution, 50 wt. % in H2O
Sigma-Aldrich
Sucrose, SAJ first grade
Sigma-Aldrich
Hexane, JIS special grade, ≥96.0%
Sigma-Aldrich
Ethylenediaminetetraacetic acid, SAJ special grade, ≥99.0%
Sigma-Aldrich
Hexane, JIS 300, ≥96.0%, for residue analysis
Sigma-Aldrich
Ethyl acetate, JIS 300, ≥99.5%, for residue analysis
Sigma-Aldrich
Ethyl acetate, JIS special grade, ≥99.5%
Sigma-Aldrich
Sucrose, JIS special grade