2′,5′-Dihydroxychalcone as a Potent Chemical Mediator and Cyclooxygenase Inhibitor

Lin, Chun‐Nan; Lee, Tai‐Hua; Hsu, Mei‐Feng; Wang, Jih‐Pyang; Ko, Feng‐Nien; Chen, Teng

doi:10.1111/j.2042-7158.1997.tb06837.x

Cited by 39 publications

(28 citation statements)

References 14 publications

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“…Chalcones (1-20; Table 1) were prepared by Claisen-Schmidt condensation of appropriate acetophenones with appropriate aromatic aldehyde [Lin et al, 1995;Hsieh et al, 1998] and dissolved in dimethyl sulfoxide (DMSO). Elemental analyses were within ± 0.4% of the theoretical values, unless otherwise noted.…”

Section: Methodsmentioning

confidence: 99%

“…We also demonstrated that chalcones inhibited release of chemical mediators from mast cells and neutrophils [Lin et al, 1995;Hsieh et al, 1998]. …”

Section: Introductionmentioning

confidence: 97%

“…Recently, we synthesized a series of chalcones and demonstrated that chalcones inhibited platelet aggregation of rabbit washed platelets and human platelet-rich plasma (PRP) induced by various inducers and cyclooxygenase activity [Lin et al, 1995]. We also demonstrated that chalcones inhibited release of chemical mediators from mast cells and neutrophils [Lin et al, 1995;Hsieh et al, 1998].…”

Section: Introductionmentioning

confidence: 98%

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Chalcones as potent antiplatelet agents and calcium channel blockers

Lin

Hsieh

et al. 2001

Drug Development Research

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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 1315 also had a potent inhibitory effect on cyclooxygenase. The selective chalcones 1216 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 Ca 2+ (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 45 Ca 2+ 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 Ca 2+ influx through both voltage-dependent and receptor-operated Ca 2+ channels. Drug Dev. Res. 53:9-14, 2001.

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Section: Methodsmentioning

confidence: 99%

“…We also demonstrated that chalcones inhibited release of chemical mediators from mast cells and neutrophils [Lin et al, 1995;Hsieh et al, 1998]. …”

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 98%

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Chalcones as potent antiplatelet agents and calcium channel blockers

Lin

Hsieh

et al. 2001

Drug Development Research

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“…They are the first isolable compounds from flavonoid biosynthesis in plants and have been reported to exhibit a diverse range of pharmacological activities including antiplatelet, antitumor, anti-inflammatory, antiplasmodial, immunosuppressant, and antioxidant properties [7] . For example, both natural and synthetic chalcones have been shown to exhibit antiplatelet activity [8,9] . Moreover, a series of polyphenolic chalcones have been demonstrated to activate heme oxygenase-1 in human endothelial cells and possibly can counteract oxidative stress [10] .…”

Section: Introductionmentioning

confidence: 99%

2′-Ethoxy-5′-Methoxy-2-(5-Methylthienyl)Chalcone Inhibits Collagen-Induced Protein Tyrosine Phosphorylation and Thromboxane Formation during Platelet Aggregation and Adhesion

Huang²,

Lin³

et al. 2009

Pharmacology

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Subendothelial collagen supports platelet adhesion, activation, and thrombus growth at sites of vascular damage. Previous studies have shown that chalcones possess antiplatelet activity, but their mechanism of action is not fully understood. In this study, a recently synthesized chalcone, 2′-ethoxy-5′-methoxy-2-(5-methylthienyl)chalcone (EMMTC), was used to investigate chalcone effects on platelet aggregation and adhesion. We found that EMMTC potently inhibited collagen-induced platelet aggregation with an IC₅₀ of 1.01 μmol/l. In contrast, it did not inhibit thrombin- and ADP-induced platelet aggregation. EMMTC could inhibit arachidonic acid (AA)-induced platelet aggregation and collagen- and AA-induced thromboxane B₂ (TXB₂) formation, suggesting that cyclooxygenase and/or thromboxane synthase were affected during this process. Moreover, EMMTC suppressed collagen-induced protein tyrosine phosphorylation, including phospholipase C-γ2 (PLC-γ2), phosphatidylinositol-3 kinase (PI-3K), Src, Fyn and LAT. Strikingly, EMMTC also blocked platelet adhesion to immobilized collagen and convulxin (a snake venom-derived protein that activates platelet glycoprotein VI receptor). The attenuation of phosphorylation of focal adhesion kinase (FAK) was observed during adhesion. Taken together, our results presented here demonstrate that the chalcone derivative EMMTC affects collagen-induced protein tyrosine phosphorylation and TXB₂ formation and functionally blocks collagen-induced platelet aggregation and adhesion.

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“…1) Previous studies showed that natural or synthetic chalcones with an inhibitory effect on arachidonic acid (AA)-induced platelet aggregation in washed rabbit platelets and secondary aggregation induced by epinephrine in human platelet-rich-plasma (PRP) are mainly mediated through the suppression of cyclooxygenase (COX) activity and reduced thromboxane formation or owing to inhibition of thromboxane synthase leading to the reduction of thromboxane formation. [2][3][4] In turn, we have also synthesized a series of 2′,5′-dimethoxylchalcone derivatives and reported as G 2 /M arrest-mediated apoptosis-inducing agents and inhibitors of nitric oxide production in rat macrophage. 5) During the past few years, COX (COX-1, COX-2) was discussed as new targets for several types of cancer, including breast cancer.…”

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confidence: 99%

Chalcone Derivatives Inhibit Human Platelet Aggregation and Inhibit Growth in Human Bladder Cancer Cells

Lin

Teng

et al. 2014

Biological & Pharmaceutical Bulletin

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In an effort to develop potent cyclooxygenase-1 (COX-1) inhibitors used as anticancer agent, a series of 2′,5′-dimethoxychalcones was screened to evaluate their antiplatelet effect on human washed platelets suspension. Compound 2 exhibited potent inhibition of human washed platelet aggregation induced by collagen, significantly inhibited collagen-and arachidonic acid-induced thromboxane B 2 release, and revealed inhibitory effect on COX-1 activity. Molecular docking studies showed that 1, 2, and 4 were bound in the active site of COX-1. These indicated that the antiplatelet effect of these compounds were mainly mediated through the suppression of COX-1 activity and reduced the thromboxane formation. To investigate the mechanistic action of COX-1 inhibitor enhanced the cytotoxic effect against human bladder cancer cells, NTUB1, we assessed the cytotoxic effect of 2 against NTUB1. Treatment of NTUB1 cells with various concentrations of 2 led to a concentration-dependent increase of cell death and decrease of reactive oxygen species levels. The flow-cytometric analysis showed that 2 induced a G1 phase cell cycle arrest but did not accompany an appreciable sub-G1 phase in NTUB1 cells. In addition, compound 2 increased p21 and p27 expressions and did not inhibit the expression of COX-1 in NTUB1 cells. Our results suggested that 2 enhanced cell growth inhibition or antiproliferative activity in NTUB1 cells through G1 arrest by COX-1 independent mechanism.

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2′,5′-Dihydroxychalcone as a Potent Chemical Mediator and Cyclooxygenase Inhibitor

Cited by 39 publications

References 14 publications

Chalcones as potent antiplatelet agents and calcium channel blockers

Chalcones as potent antiplatelet agents and calcium channel blockers

2′-Ethoxy-5′-Methoxy-2-(5-Methylthienyl)Chalcone Inhibits Collagen-Induced Protein Tyrosine Phosphorylation and Thromboxane Formation during Platelet Aggregation and Adhesion

Chalcone Derivatives Inhibit Human Platelet Aggregation and Inhibit Growth in Human Bladder Cancer Cells

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