A review of anti-infective and anti-inflammatory chalcones.

Chalcones with 2‘,3‘,4‘-trimethoxy, 2‘,4‘-dimethoxy, 4‘-methoxy, 4‘-ethoxy, 2‘,4‘-dihydroxy, and 4‘-hydroxy groups on ring B were synthesized and evaluated in vitro against Plasmodium falciparum (K1) in a [3H] hypoxanthine uptake assay. The other ring A was quinoline, pyridine, naphthalene, or phenyl rings with electron-donating or electron-withdrawing substituents of varying lipophilicities. Trimethoxy 6 and 27, dimethoxy 7, 8, 29, and methoxy 31 analogues had good in vitro activities (IC50 < 5 μM). 3-Quinolinyl ring A derivatives were well represented among the active compounds. Hydroxylated chalcones were less active than the corresponding alkoxylated analogues. When evaluated in vivo, 8 and 208 were comparable to chloroquine in extending the lifespan of infected mice. Multivariate data analysis showed that in vitro activity was mainly determined by the properties of ring B. Quantitative structure−activity relationship models with satisfactory predictive ability were obtained for various B ring chalcon...

Antimalarial Alkoxylated and Hydroxylated Chalones: Structure−Activity Relationship Analysis

Anticancer activities of novel chalcone and bis-chalcone derivatives

Flavones: An important scaffold for medicinal chemistry

Hydroxyapatite: A review of syntheses, structure and applications in heterogeneous catalysis☆

Purpose. Mast cell and neutrophil degradations are the important players in inflammatory disorders. Combined with potent inhibition of chemical mediators released from mast cells and neutrophil degranulations, it could be a promising anti-inflammatory agent. 2′,5′-Dihydroxychalcone has been reported as a potent chemical mediator and cyclooxygenase inhibitor. In an effort to continually develop potent anti-inflammatory agents, a novel series of chalcone, 2′- and 3′-hydroxychalcones, 2′,5′-dihydroxychalcones and flavanones were continually synthesized to evaluate their inhibitory effects on the activation of mast cells and neutrophils and the inhibitory effect on phlogist-induced hind-paw edema in mice.

Synthesis and anti-inflammatory effect of chalcones and related compounds.

The process of degranulation of mast cells and neutrophils contributes to inflammatory disorders. Activation of microglial cells and macrophages is believed to be involved in inflammatory, infectious and degenerative diseases of the CNS. Combining the potent inhibition of chemical mediators released by the degranulation of mast cells or neutrophils and from the activated microglial cells or macrophages, would lead to a promising anti-inflammatory agent for the treatment of peripheral and central inflammation. A series of chalcone derivatives have been reported to have potent anti-inflammatory activity. In an effort to continually develop potent anti-inflammatory agents, novel series of chalcones, 2'-hydroxy- and 2',5'-dihydroxychalcones were synthesized and their inhibitory effects on the activation of mast cells, neutrophils, microglial cells and macrophages were evaluated in-vitro. The chalcones were prepared by Claisen-Schmidt condensation of appropriate acetophenones with an appropriate aromatic aldehyde. The alkoxychalcones were prepared with appropriate hydroxychalcones and alkyl iodide and the dihydroxychalcones were prepared by hydrogenation of an appropriate chalcone with Pd/C. Almost all of the hydroxychalcones exhibited potent inhibitory effects on the release of beta-glucuronidase and lysozyme from rat neutrophils stimulated with formyl-Met-Leu-Phe/cytochalasin B (fMLP/CB). Of the hydroxychalcones, compound 1 was the most potent inhibitor of the release of beta-glucuronidase (IC50=1.6+/-0.2 microM) and lysozyme (IC50=1.4+/-0.2 microM) from rat neutrophils stimulated with fMLP/CB. Almost all of the 2',5'-dialkoxychalcones exhibited potent inhibitory effects on nitric oxide (NO) formation from murine microglial cell lines N9 stimulated with lipopolysaccharide (LPS). Of these, compound 11 showed the greatest effect (IC50=0.7+/-0.06 microM). The present results demonstrated that most of the chalcone derivatives have an anti-inflammatory effect. The inhibitory effects of dialkoxychalcones, 10-12 on inflammation are probably not due to the inhibition of mast cells and neutrophil degranulation, but are mediated through the suppression of NO formation from N9 cells.

Synthesis and anti-inflammatory effect of chalcones.

A series of xanthone derivatives was synthesized and tested in-vitro for their ability to inhibit aggregation of rabbit washed platelets and human platelet-rich plasma (PRP) induced by various inducers.



2-Prenyloxyxanthone showed the most potent inhibition of rabbit washed platelet aggregation induced by arachidonic acid (IC50 = 10.2 μM). Of the compounds tested in human PRP, 2-[3 (propylamino)-2-hydroxypropoxy]xanthone (4) hydrochloride salt exhibited the most potent inhibition of platelet aggregation induced by adrenaline (IC50 = 4.4 μM), whereas in evaluation of mouse antithrombotic activity, compound 4 exhibited the most potent protection of mice from thrombotic challenge. Compound 4, 2-[3-(isopropylamino)-2-hydroxypropoxylxanthone hydrochloride salt and 2,5 dihydroxyxanthone suppressed the secondary aggregation induced by adrenaline in human PRP.



We conclude that the antiplatelet effects of these compounds are mainly due to an inhibitory effect on thromboxane formation.

Synthesis and antithrombotic effect of xanthone derivatives.

In an effort to continually develop potent antiplatelet agents with vasorelaxing and antiinflammatory actions, a novel series of antiinflammatory chalcones was continually screened to evaluate their antiplatelet and vasorelaxing effects. Their structure–activity relationships and mode of action were discussed and characterized. A novel series of antiinflammatory chalcones was studied on antiplatelet effect in rabbit washed platelets and human platelet-rich plasma (PRP) and vasorelaxing effect in rat thoracic aorta. Arachidonic acid-induced platelet aggregation was potently inhibited by almost all the chalcone derivatives and 13–15 also had a potent inhibitory effect on cyclooxygenase. The selective chalcones 12–16 tested in human PRP significantly inhibited secondary aggregation induced by adrenaline. In rat thoracic aorta, most of chalcones at high concentration significantly depressed the contractions induced by Ca2+ (1.9 mM) in high K+ (80 mM) medium and the phasic and tonic contractions caused by norepinephrine (3 μM). In the rat thoracic aorta, the phenylephrine- and high K+-induced 45Ca2+ influx were both inhibited by a selective chalcone derivative, 14. These results indicate that the antiplatelet actions of chalcones are mainly mediated through the suppression of cyclooxygenase activity and reduced thromboxane formation and their inhibitory effects on the contractile response caused by high K+ and norepinephrine in rat thoracic aorta are mainly due to inhibition of Ca2+ influx through both voltage-dependent and receptor-operated Ca2+ channels. Drug Dev. Res. 53:9–14, 2001. © 2001 Wiley-Liss, Inc.

Chalcones as potent antiplatelet agents and calcium channel blockers

In an effort to develop potent antiplatelet agents with anti-inflammatory action, a novel series of anti-inflammatory chalcones was screened to evaluate their antiplatelet effects. Structure-activity relationships and mode of action were investigated and characterized. The antiplatelet effects of the chalcones on washed rabbit platelets and human platelet-rich plasma were evaluated. Arachidonic acid-induced platelet aggregation was potently inhibited by almost all the chalcone derivatives. Collagen-induced platelet aggregation was potently inhibited by all the chalcone derivatives at 300 microM, except for compound 4 at 100 microM. Compounds 6, 7 and 9 significantly inhibited the aggregation of washed rabbit platelets induced by platelet-activating factor at 300 microM. Of the compounds tested in human platelet-rich plasma, compounds 2, 8 and 9 showed significant inhibition of secondary aggregation induced by adrenaline. It is concluded that the antiplatelet effect of 2, 8 and 9 is mainly owing to an inhibitory effect on thromboxane formation. The inhibitory effect of 6, 7 and 9 on platelet aggregation induced by platelet-activating factor could be owing to a calcium antagonizing effect or inhibition of intracellular calcium mobilization.

Hsin-Kaw Hsieh

Papers

Synthesis and anti-inflammatory effect of chalcones and related compounds.

Synthesis and anti-inflammatory effect of chalcones.

Synthesis and antithrombotic effect of xanthone derivatives.

Chalcones as potent antiplatelet agents and calcium channel blockers

Structure-activity relationship studies on chalcone derivatives: potent inhibition of platelet aggregation.