Inhibition of prostaglandin E2 production by 2′-hydroxychalcone derivatives and the mechanism of action

Abstract

The effects of 14 synthetic 2'-hydroxychalcone derivatives on prostaglandin E2 (PGE2) production in rat peritoneal macrophages stimulated by the protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (TPA), were examined to clarify the structure-activity relationship. 2',4-Dihydroxy-4'-methoxychalcone (compound 3), 2',4-dihydroxy-6'-methoxychalcone (compound 8) and 2'-hydroxy-4'-methoxychalcone (compound 9) suppressed PGE2 production more potently than the other compounds. The IC50 (50% Inhibitory concentration) value for compounds 3, 8 and 9 was calculated to be 3 microM. The activity of cyclooxygenase (COX)-1 was inhibited slightly by compound 9, but that of COX-2 was not inhibited. At concentrations that inhibited the production of PGE2, compound 9 had no effect on the release of radioactivity from [3H]arachidonic acid-labelled macrophages stimulated by TPA. Western-blot analysis revealed that the induction of COX-2 protein by TPA was inhibited by compound 9 in parallel with the inhibition of PGE2 production. Compounds 3 and 8 had similar effects. These findings suggest that 4'-methoxyl and 6'-methoxyl groups are required for the expression of more potent inhibitory activity against PGE2 production, and that the inhibition of PGE2 production by these 2'-hydroxychalcone derivatives is due to the inhibition of TPA-induced COX-2 protein expression.

Hydroxychalcones exhibit differential effects on XRE transactivation

“…Among them, 2 -hydroxyl substituted chalcones have attracted much attention because they can prevent platelet aggregation (Lin et al, 1997), polymixin B-induced edema (Hsieh et al, 1998), LPSinduced septic shock (Batt et al, 1993), and glomerulonephritis (Hayashi et al, 1996) in animal models. 2 -Hydroxychalcone can also suppress the adhesion of activated neutrophils to HUVEC cell cultures (Madan et al, 2000), and its derivatives are inhibitors of TPAinduced COX-2 expression in rat macrophages (Kim et al, 2001).…”

Organic Crystals with Near‐Infrared Amplified Spontaneous Emissions Based on 2′‐Hydroxychalcone Derivatives: Subtle Structure Modification but Great Property Change

“…The D-A structure,i ntramolecular H-bond with ESIPT nature, slip-packing structure and molecular planarization effectively make the crystals 1-3 highly emissive in the deep red/NIR region. To explore the emission mechanism of crystals 1-3, [10] All the compounds are synthesized according to the literature. [11] We obtained red crystals with centimeter-scale size and slab-like shape based on 1-3.Asshown in Figure 1, the crystals display bright deep red to NIR fluorescence (l em = 680-716 nm; F f = 0.25-0.32), although their solutions are almost non-emissive (F f < 0.01).…”

Therapeutic Potential of Natural Products from Terrestrial Plants as TNF-&alpha; Antagonist

“…This compound was initially isolated from the seeds of Amomum subulatum and subsequently from other zingiberous plant species. The SAR studies of chalcones showed that among 2'-hydroxychalcone derivatives a methoxy group at 4' and 6' is essential for the expression of PGE 2 inhibitory activity and substitution of the B ring is not essential for the activity [28]. Cardamonin is active despite the absence of functional group substitution on the B ring, it has a methoxy substitution on the 6' position of A ring.…”