Structure and antiinflammatory activity relationships of wogonin derivatives

Abstract

A number of wogonin derivatives have been synthesized as congeners of wogonin and evaluated for their inhibitory activities of PGE2 production. Wogonin derivatives modified at the B ring of wogonin were obtained from 2,4-Dihydroxy-3,6-dimethoxyacetophenone (1) via several steps. Most wogonin derivatives exhibited much reduced inhibitory activities against COX-2 catalyzed PGE2 production compared to that of wogonin. Alkylation of 5,7-phenol groups and substitution at the B ring of wogonin generally caused reduction of inhibitory activity.

Recent developments in anti‐inflammatory natural products

“…Chrysin (139) showed the preventing effect in COX-2 suppression and in inhibiting the platelet aggregation. 19 The various chrysin analogs modulated the activity, as well as the expression of COX-2 and iNOS enzymes.…”

“…22 Wogonin is reported to inhibit the NO and PGE 2 production and induction of iNOS and COX-2 in LPS-activated RAW cells. 6 Jang et al 139 synthesized some wogonin analogs and evaluated their activity against COX-2 catalyzed PGE 2 production. Most of the analogs were less active than wogonin.…”

Structural Alterations of Wogonin Significantly Reduce the Inhibitory Activity against COX-2 Catalyzed PGE2Production from LPS-Induced RAW 264.7 Cells

“…It was already reported that the functional group replacement at the 8-position of wogonin from methoxy to aryl group caused loss of inhibitory activity (Dao et al, 2004b). Similarly, the Wogonin derivatives modified at the B-ring of Wogonin exhibited much reduced inhibitory activities against COX-2 catalyzed PGE2 production compared to that of wogonin (Jang et al, 2005). In spite of the structural similarity between chrysin and wogonin, wogonin exhibited much stronger inhibitory activity than chrysin against COX-2 catalyzed PGE2 production from LPS-treated RAW 264.7 cells (Dao et al, 2004a) Therefore, these precedent results led us to carry out the structure alteration at the A-ring of wogonin to observe the effect of each substituent.…”

“…Flavones for the inhibitory activity tests were prepared following the procedure as described in the precedent literatures (Dao et al, 2004a;Jang et al, 2005). Thus, commercially available desired hydroxyacetopheones were selectively protected and were reacted with appropriately substituted aryl aldehydes to yield the corresponding chalcones.…”

“…Chrysin (3) was purchased from Sigma-Aldrich Korea and used for the bioassay without further purification. Wogonin for test was previously synthesized by us (Jang et al, 2005) and fully characterized. C-NMR (100 MHz, CDCl3): δ 179.8 (C-4), 164.3 (C-2), 151.7 (C-7), 146.2 (C-9), 134.9 (C-8), 131.9 (C-1'), 131.9 (C-4'), 129.2 (C-3', C-5'), 126.8 (C-2', C-6'), 118.4 (C-5), 115.9 (C-10), 109.7 (C-6), 106.3 (C-3), 56.6 (C-OMe).…”