Deep vein thrombosis (DVT) associates with considerable morbidity, functional disability and mortality. Due to the lack of suitable inhibitor the correlation of various factors in DVT onset remains unknown. In this context we analyzed the structure of anti-platelet aggregation agent,
P-selectin down-regulator, GPIIb/IIIa down-regulator and
anti-inflammatory agent, thereby designed N-(3S-1,2,3,4-tetrahydroisoquinoline-3-carbonyl)- Thr-Ala-
Arg-Gly-Asp(Val)-Val (
IQCA-TAVV) as an inhibitor of DVT to receive evaluations. The docking predicted that
IQCA-TAVV can target
P-selectin and GPIIb/IIIa. The UV showed that
IQCA-TAVV can act on
P-selectin and GPIIb/IIIa. ELISA indicated that
IQCA-TAVV concentration dependently inhibited activated platelets to express
P-selectin and GPIIb/IIIa, and the minimal effective concentration was 1 nM. IC50 of
IQCA-TAVV against platelet aggregation induced by
arachidonic acid,
adenosine diphosphate and
platelet activating factor fell within a range of 0.13 nM to 0.30 nM. In vivo
IQCA-TAVV dose-dependently inhibited
venous thrombosis and the minimal effective dose was 1 nmol/kg. On ear
edema model the anti-
inflammation activity of 10 nmol/kg
IQCA-TAVV equaled that of 1.1mmol/kg
aspirin. The concentration of
IL-2,
IL-6 and
IL-8 in the serum of the ear
edema mice were also significantly decreased by 10 nmol/kg
IQCA-TAVV. Even at 1 μmol/kg of dose
IQCA-TAVV still did not injure the kidney, the liver, and the nerves of healthy mice. Thereby
IQCA-TAVV depicts a relationship of three levels (inhibiting platelet activation, targeting externalized membrane receptor, decreasing serum inflammatory factor) for the down-regulation of
P-selectin, GPIIb/IIIa,
IL-2,
IL-6 and
IL-8 in DVT.