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Antithrombotic and antiplatelet activities of 2-chloro-3-[4- (ethylcarboxy)-phenyl]-amino-1,4-naphthoquinone (NQ12), a newly synthesized 1,4-naphthoquinone derivative
- Antithrombotic and antiplatelet activities of 2-chloro-3-[4- (ethylcarboxy)-phenyl]-amino-1,4-naphthoquinone (NQ12), a newly synthesized 1,4-naphthoquinone derivative
- Yuk D.-Y.; Ryu C.-K.; Hong J.-T.; Chung K.-H.; Kang W.-S.; Kim Y.; Yoo H.-S.; Lee M.-K.; Lee C.-K.; Yun Y.-P.
- Ewha Authors
- SCOPUS Author ID
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- Journal Title
- Biochemical Pharmacology
- vol. 60, no. 7, pp. 1001 - 1008
- SCI; SCIE; SCOPUS
- The possibility of NQ12 (2-chloro-3-[4-(ethylcarboxy)-phenyl]-amino-1,4- naphthoquinone) as a novel antithrombotic agent and its mode of action were investigated. The effects of NQ12 on platelet aggregation in human platelet- rich plasma in vitro, in rats ex vivo, and on murine pulmonary thrombosis in vivo, as well as the mode of antithrombotic action were examined. NQ12 potently inhibited ADP-, collagen-, epinephrine-, and calcium ionophore- induced human platelet aggregations in vitro concentration-dependently. NQ12 significantly inhibited rat platelet aggregation in an ex vivo study. NQ12 prevented murine pulmonary thrombosis in a dose-dependent manner. However, NQ12 did not affect coagulation parameters such as activated partial thromboplastin time, prothrombin time, and thrombin time. NQ12 inhibited fibrinogen binding to the platelet surface GPIIb/IIIa receptor, but failed to inhibit binding to the purified GPIIb/IIIa receptor. Thromboxane B2 formation caused by thrombin or collagen was inhibited significantly by NQ12. The phosphoinositide breakdown induced by thrombin or collagen was inhibited concentration-dependently by NQ12. These results suggest that NQ12 may be a promising antithrombotic agent, and its antithrombotic activity may be due to antiplatelet aggregation activity, which may result from the inhibition of phosphoinositide breakdown and thromboxane A2 formation. (C) 2000 Elsevier Science Inc.
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