5-LIPOXYGENASE INHIBITOR CAFFEIC ACID ATTENUATES Ca2+ RESPONSES, INDUCED BY TRIFLUOPERAZINE IN MACROPHAGES

Leukotrienes are inflammatory mediators that actively participate in the inflammatory response and host defense against pathogens. However, leukotrienes also participate in chronic inflammatory diseases. 5-lipoxygenase is a key enzyme in the biosynthesis of leukotrienes and is thus a validated therapeutic target. As of today, zileuton remains the only clinically approved 5-lipoxygenase inhibitor; however, its use has been limited due to severe side effects in some patients. Hence, the search for a better 5-lipoxygenase inhibitor continues. In this study, we investigated structural analogues of caffeic acid phenethyl ester, a naturally-occurring 5-lipoxygenase inhibitor, in an attempt to enhance the inhibitory activity against 5-lipoxygenase and determine structure-activity relationships. These compounds were investigated for their ability to attenuate the biosynthesis of leukotrienes. Compounds 13 and 19, phenpropyl and diphenylethyl esters, exhibited significantly enhanced inhibitory activity when compared to the reference molecules caffeic acid phenethyl ester and zileuton.

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P3276 Cardioprotective effect of lipoxygenase inhibitor Quercetin in acute myocardial infarction with left-ventricular heart failure

European Heart Journal ◽

10.1016/s0195-668x(03)95902-1 ◽

2003 ◽

Vol 24 (5) ◽

pp. 620

Author(s):

S KOZHUKHOV

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Acute Myocardial Infarction ◽

Left Ventricular ◽

Cardioprotective Effect ◽

Lipoxygenase Inhibitor

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Platelet Aggregation in Whole Blood: The Role of Thromboxane A2 and Adenosine Diphosphate

Thrombosis and Haemostasis ◽

10.1055/s-0038-1660081 ◽

1985 ◽

Vol 54 (03) ◽

pp. 612-616 ◽

Cited By ~ 17

Author(s):

A J Carter ◽

S Heptinstall

Keyword(s):

Platelet Aggregation ◽

Whole Blood ◽

Adenosine Diphosphate ◽

Blood Platelet ◽

Thromboxane B2 ◽

Lipoxygenase Inhibitor ◽

Thromboxane Synthase Inhibitor ◽

Synthase Inhibitor

SummaryThe platelet aggregation that occurred in whole blood in response to several aggregating agents (collagen, arachidonic acid, adenosine diphosphate, adrenaline and thrombin) was measured using an Ultra-Flo 100 Whole Blood Platelet Counter. The amounts of thromboxane B2 produced were measured by radioimmunoassay. The effects of various inhibitors of thromboxane synthesis and the effects of apyrase, an enzyme that destroys adenosine diphosphate, were determined.Platelet aggregation was always accompanied by the production of thromboxane B2, and the amounts produced depended on the nature and concentration of the aggregating agent used. The various inhibitors of thromboxane synthesis - aspirin and flurbiprofen (cyclo-oxygenase inhibitors), BW755C (a cyclo-oxygenase and lipoxygenase inhibitor) and dazoxiben (a selective thromboxane synthase inhibitor) - did not markedly inhibit aggregation. Results obtained using apyrase showed that adenosine diphosphate contributed to the aggregation process, and that its role must be acknowledged when devising means of inhibiting platelet aggregation in vivo.

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