Antithrombotic and antiplatelet activities of 2-chloro-3-[4-(ethylcarboxy)-phenyl]-amino-1,4-naphthoquinone (NQ12), a newly synthesized 1,4-naphthoquinone derivative.

Abstract

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 B(2) 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 A(2) formation.

• Authors: D Y Yuk, C K Ryu, J T Hong, K H Chung, W S Kang, Y Kim, H S Yoo, M K Lee, C K Lee, Y P Yun
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 60 Issue 7 Pg. 1001-8 (Oct 01 2000) ISSN: 0006-2952 [Print] England
• PMID: 10974210 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2-chloro-3-((4-ethyl-phenyl)-amino)-1,4-naphthalendione
• Fibrinolytic Agents
• Inositol Phosphates
• Naphthalenes
• Platelet Aggregation Inhibitors
• Platelet Glycoprotein GPIIb-IIIa Complex
• inositol 1,2,3-trisphosphate
• Thromboxane B2

Topics

• Animals
• Blood Coagulation (drug effects)
• Blood Platelets (drug effects, metabolism)
• Disease Models, Animal
• Fibrinolytic Agents (chemical synthesis, chemistry, pharmacology, therapeutic use)
• Inositol Phosphates (metabolism)
• Male
• Mice
• Mice, Inbred ICR
• Naphthalenes (chemical synthesis, chemistry, pharmacology, therapeutic use)
• Platelet Aggregation (drug effects)
• Platelet Aggregation Inhibitors (chemical synthesis, chemistry, pharmacology, therapeutic use)
• Platelet Glycoprotein GPIIb-IIIa Complex (drug effects, metabolism)
• Pulmonary Embolism (prevention & control)
• Rats
• Rats, Sprague-Dawley
• Thromboxane B2 (metabolism)