Jirasek, Petr and Amslinger, Sabine and Heilmann, Joerg (2014) Synthesis of Natural and Non-natural Curcuminoids and Their Neuroprotective Activity against Glutamate-Induced Oxidative Stress in HT-22 Cells. JOURNAL OF NATURAL PRODUCTS, 77 (10). pp. 2206-2217. ISSN 0163-3864, 1520-6025
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A strategy for the synthesis of natural and non-natural 5-deoxy-6,7-dihydrocurcuminoids (diarylheptanoids) was developed for the preparation of 14 compounds with varying aromatic substituent patterns and a different functionality in the aliphatic seven-carbon chain. The in vitro protective activity against glutamate-induced neuronal cell death was examined in the murine hippocampal cell line HT-22 to find structural motifs responsible for neuroprotective effects in vitro. Among the tested compounds the ferulic acid-like unit, present in the structures of (E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hept-1-en-3-one (5) and (E)-1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)hept-1-en-3-one (7), appeared to be an important feature for protection against glutamate-induced neurotoxicity. Both compounds demonstrated significant neuroprotective activity in a concentration range between 1 and 25 mu M without showing toxic effects in a cytotoxicity assay with HT-22 cells. Furthermore, (E)-1,7-bis(3,4-dihydroxyphenyl)hept-1-en-3-one (9), exhibiting a caffeic acid-like structural motif, displayed a neuroprotective activity at a nontoxic concentration of 25 mu M. In contrast, (1E,6E)-1,7-bis(3,4-dihydroxyphenyl)hepta-1,6-diene-3,5-dione (4, di-O-demethylcurcumin) showed mainly cytotoxic effects. A corresponding single-ring analogue that contains the ferulic acid-like unit as an enone was not active.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PHASE-1 METABOLITES; ALZHEIMERS-DISEASE; TETRAHYDROCURCUMIN; DERIVATIVES; ANALOGS; KINASE; RAT; BISDEMETHOXYCURCUMIN; 5-LIPOXYGENASE; IDENTIFICATION; |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Biology (Prof. Heilmann) Chemistry and Pharmacy > Institut für Organische Chemie > Arbeitskreis Dr. Sabine Amslinger |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Aug 2019 13:20 |
| Last Modified: | 12 Aug 2019 13:20 |
| URI: | https://pred.uni-regensburg.de/id/eprint/9408 |
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