Sun, Qiu and Schmidt, Sebastian and Tremmel, Martina and Heilmann, Joerg and Koenig, Burkhard (2014) Synthesis of natural-like acylphloroglucinols with anti-proliferative, anti-oxidative and tube-formation inhibitory activity. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 85. pp. 621-628. ISSN 0223-5234, 1768-3254
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Two series of natural and natural-like mono- and bicyclic acylphloroglucinols derived from secondary metabolites in the genus Hypericum (Hypericaceae) were synthesised and tested in vitro for anti-proliferative and tube-formation inhibitory activity in human microvascular endothelial cells (HMEC-1). In addition, their anti-oxidative activity was determined via an ORAC-assay. The first series of compounds (4a-e) consisted of geranylated monocyclic acylphloroglucinols with varying aliphatic acyl substitution patterns, which were subsequently cyclised to the corresponding 2-methyl-2-prenylchromane derivatives (5a and 5d). The second series involved compounds containing a 2,2-dimethylchromane skeleton with differing aromatic acyl substitution (6a-d and 7a-e). Compound 7a, (5,7-dihydroxy-2,2-dimethylchroman-6-yl)-(3,4-dihydroxyphenyl)methanone), showed the highest in vitro anti-proliferative activity with an IC50 of 0.88 +/- 0.08 mu M and a remarkable anti-oxidative activity of 2.8 +/- 0.1 TE from the ORAC test. Interestingly, the high anti-proliferative activity of these acylphloroglucinols was not associated with tube-formation inhibition. Compounds (E)-1-(3-(3,7-dimethylocta-2,6-dien-1-yl)-2,4,6-trihydroxyphenyl)-2-methylbutan-1-one (4d) and (5,7-dihydroxy-2,2-dimethylchroman-6-yl)(3,4-dimethoxyphenyl)methanone (6a) exhibited moderate to weak anti-proliferative effects (IC50 11.0 +/- 1 mu M and 48.0 +/- 43 mu M, respectively) and inhibited the capillary-like tube formation of HMEC-1 in vitro, whereas 7a was inactive. The most active compound in the ORAC assay was 7c, which exhibited an anti-oxidative effect of 6.6 +/- 1.0 TE. However, this compound showed only weak activity during the proliferation assay (IC50 53.8 +/- 0.3) and did not inhibit tube-formation. (C) 2014 Elsevier Masson SAS. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ST-JOHNS-WORT; PHLOROGLUCINOL DERIVATIVES; HYPERICUM-PAPUANUM; IN-VITRO; HYPERFORIN; ANTIBACTERIAL; EMPETRIFOLIUM; CYTOTOXICITY; CHALCONES; SKELETON; Acylphloroglucinol; Chromane; HMEC-1; Anti-proliferative activity; Tube formation; ORAC |
| 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 > Lehrstuhl Prof. Dr. Burkhard König |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Aug 2019 08:26 |
| Last Modified: | 12 Aug 2019 08:26 |
| URI: | https://pred.uni-regensburg.de/id/eprint/9363 |
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