Studies on the antithrombotic and antiplatelet activities of NQ304, a newly synthesized naphthoquinone derivative

Abstract

The effect of NQ304 (2-chloro-3-(4-hexylphenyl)-amino-1,4-naphthoquinone) as a novel antithrombotic agent was investigated. NQ304 was found to inhibit platelet aggregation in human platelets in vitro and in rat ex vivo, and murine pulmonary thrombosis in vivo. NQ304 potently inhibited adenosine diphosphate (ADP), collagen, epinephrine and calcium ionophore-induced human platelet aggregation in vitro dose-dependently. In the ex vivo study, oral administration of NQ304 significantly inhibited platelet aggregation in rats. However, NQ304: was found not to affect the coagulation system, since it did not change the prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT), The agent prevented death due to pulmonary thrombosis by the platelet aggregates in mice in vivo. In the mouse tail bleeding time test, NQ304 showed a significant prolongation of the tail bleeding time in conscious mice. These results suggest that a principal antithrombotic effect of NQ304 may be due to the antiplatelet aggregation activity but not to anticoagulation activity.