| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1397707 | European Journal of Medicinal Chemistry | 2010 | 8 Pages |
Besides 2′,4′-dihydroxy-4,6′-dimethoxy-3′-prenylchalcone (1) and 4-acetoxy-2′,4′-dihydroxy-6′-methoxy-3′-prenylchalkon (2), both phase II metabolites of xanthohumol in rats, also a principally new chalcone 3′-coumaroyl-2′,4,4′-trihydroxy-6′-methoxychalcone (3), structurally derived from helichrysetin (4) by introducing a second coumaroyl substructure at C-3′ was synthesized. Furthermore new chalcones were synthesized by combination of the B-Ring fragments of helichrysetin, xanthohumol, xanthohumol C and xanthohumol H with ferulic or caffeic acid moieties in Ring A. Compound 3 showed the highest cytotoxic activity against HeLa cells with an IC50 value of 7.3 ± 0.4 μM. Anti-oxidative effects were determined in the ORAC assay and revealed very strong activity for 3 and 3-methoxyhelichrysetin (6) exhibiting 7.7 ± 0.3 and 6.0 ± 1.3 Trolox equivalents, respectively. The anti-inflammatory activity of all compounds was measured in an in vitro ICAM-1 assay with human microvascular endothelial cells (HMEC-1) and compared with the activity of other structurally related chalcones. The results showed increasing anti-inflammatory activity for the new synthetic chalcones exhibiting a caffeoyl substructure with 3-hydroxyhelichrysetin (5) and 3-hydroxyxanthohumol H (14) being the most active. At 10 μM the TNFα induced expression of ICAM-1 was significantly reduced to 65.8 and 69.6% of control, respectively.
Graphical abstractSeveral new chalcones based on the natural compounds helichrysetin and xanthohumol were synthesized and characterized concerning their anti-inflammatory, cytotoxic and anti-oxidative activity.Figure optionsDownload full-size imageDownload as PowerPoint slide
