Ruecker, Hannelore and Al-Rifai, Nafisah and Rascle, Anne and Gottfried, Eva and Brodziak-Jarosz, Lidia and Gerhaeuser, Clarissa and Dick, Tobias P. and Amslinger, Sabine (2015) Enhancing the anti-inflammatory activity of chalcones by tuning the Michael acceptor site. ORGANIC & BIOMOLECULAR CHEMISTRY, 13 (10). pp. 3040-3047. ISSN 1477-0520, 1477-0539
Full text not available from this repository. (Request a copy)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, alpha-X-substituted 2', 3,4,4'-tetramethoxychalcones (alpha-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 alpha-X-TMCs while for NF-kappa B it was inhibited. For most alpha-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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NF-KAPPA-B; HEME OXYGENASE-1; SULFHYDRYL-GROUPS; TARGET GENES; NITRIC-OXIDE; MACROPHAGES; TRANSCRIPTION; REACTIVITY; ENZYMES; CELLS; |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Chemistry and Pharmacy > Institut für Organische Chemie > Arbeitskreis Dr. Sabine Amslinger |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Jul 2019 13:05 |
| Last Modified: | 23 Jul 2019 13:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5790 |
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