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Inhibitory effects of J78, a newly synthesized 1,4-naphthoquinone derivative, on experimental thrombosis and platelet aggregation
- Inhibitory effects of J78, a newly synthesized 1,4-naphthoquinone derivative, on experimental thrombosis and platelet aggregation
- Jin Y.-R.; Ryu C.-K.; Moon C.-K.; Cho M.-R.; Yun Y.-P.
- Ewha Authors
- SCOPUS Author ID
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- vol. 70, no. 4, pp. 195 - 200
- SCI; SCIE; SCOPUS
- Several compounds with the backbone of 1,4-naphthoquinone chemical structure have been reported to display antiplatelet and antithrombotic activities, indicating that this congener compound may be a new source in the antithrombotic drug development. In the present study, the possible antiplatelet activity and antithrombotic efficacy of J78 (2-chloro-3-[2′- bromo, 4′-fluorophenyl]-amino-8-hydroxy-1,4-naphthoquinone), a newly synthesized 1,4-naphthoquinone derivative, were examined. Orally administered J78 (50, 100 mg/kg) dose dependently protected mice against the collagen + epinephrine-induced thromboembolic death. Orally administered J78 also significantly inhibited the ADP- and collagen-induced rat platelet aggregation ex vivo, with inhibition values of 44 and 40%, respectively. J78 inhibited the collagen-, arachidonic acid- and thrombin-induced human platelet aggregation concentration dependently in vitro, with IC 50 values of 7.8 ± 0.4, 10.1 ± 0.4 and 18.4 ± 2.0 μmol/l, respectively. It was also active in inhibiting Ca 2+ ionophore, A23187-induced platelet aggregation, suggesting that J78 may have an inhibitory effect on Ca 2+ mobilization. J78, however, did not alter coagulation parameters such as activated partial thromboplastin time and prothrombin time in human plasma. Taken together, these results suggest that J78 may be a promising antithrombotic agent, and its antithrombotic activity may be due to antiplatelet rather than anticoagulation activity. Copyright © 2004 S. Karger AG, Basel.
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