Al-Rifai, Nafisah and Ruecker, Hannelore and Amslinger, Sabine (2013) Opening or Closing the Lock? When Reactivity Is the Key to Biological Activity. CHEMISTRY-A EUROPEAN JOURNAL, 19 (45). pp. 15384-15395. ISSN 0947-6539, 1521-3765
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Thiol-mediated processes play a key role to induce or inhibit inflammation proteins. Tailoring the reactivity of electrophiles can enhance the selectivity to address only certain surface cysteines. Fourteen 2,3,4,4-tetramethoxychalcones with different -X substituents (X=H, F, Cl, Br, I, CN, Me, p-NO2-C6H4, Ph, p-OMe-C6H4, NO2, CF3, COOEt, COOH) were synthesized, containing the potentially electrophilic ,-unsaturated carbonyl unit. The assessment of their reactivity as electrophiles in thia-Michael additions with cysteamine shows a change in the reactivity of more than six orders of magnitude. Moreover, a clear correlation between their reactivity and an influence on the inflammation proteins heme oxygenase-1 (HO-1) and the inducible NO synthase (iNOS) is demonstrated. As the biologically most active compound, the -CF3-chalcone is shown to inhibit the NO production in RAW264.7 mouse macrophages in the nanomolar range.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MICHAEL ACCEPTORS; ACID-DERIVATIVES; CHALCONES; TRIFLUOROMETHYLATION; INHIBITORS; COVALENT; chalcones; electrophiles; inflammation proteins; reactivity tuning; thiols |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institut für Organische Chemie > Arbeitskreis Dr. Sabine Amslinger |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 25 Mar 2020 12:21 |
| Last Modified: | 25 Mar 2020 12:21 |
| URI: | https://pred.uni-regensburg.de/id/eprint/15688 |
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