Inhibitory effects of J78, a newly synthesized 1,4-naphthoquinone derivative, on experimental thrombosis and platelet aggregation.

Abstract

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'-fluoro- phenyl]-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 micromol/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.

• Authors: Yong-Ri Jin, Chung-Kyu Ryu, Chang-Kiu Moon, Mi-Ra Cho, Yeo-Pyo Yun
• Journal: Pharmacology (Pharmacology) Vol. 70 Issue 4 Pg. 195-200 (Apr 2004) ISSN: 0031-7012 [Print] Switzerland
• PMID: 15001820 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2004 S. Karger AG, Basel

Chemical References

• 2-chloro-3-(2'-bromo-4'-fluorophenyl)amino-8-hydroxy-1,4-naphthoquinone
• Fibrinolytic Agents
• Naphthoquinones
• Vasoconstrictor Agents
• Adenosine Diphosphate
• Collagen
• L-Lactate Dehydrogenase
• Epinephrine

Topics

• Adenosine Diphosphate (pharmacology)
• Animals
• Collagen
• Epinephrine
• Fibrinolytic Agents (pharmacology, therapeutic use)
• Humans
• In Vitro Techniques
• L-Lactate Dehydrogenase (metabolism)
• Male
• Mice
• Naphthoquinones (pharmacology, therapeutic use)
• Partial Thromboplastin Time
• Platelet Aggregation (drug effects)
• Pulmonary Embolism (blood, chemically induced, drug therapy)
• Rats
• Rats, Sprague-Dawley
• Vasoconstrictor Agents