Hsien-Cheng Lin

Synthesis and Antithrombotic Effect of Xanthone Derivatives

A series of xanthone derivatives was synthesized and tested in‐vitro for their ability to inhibit aggregation of rabbit washed platelets and human platelet‐rich plasma (PRP) induced by various inducers.

Chemistry and biological activities of constituents from Morus australis.

A novel constituent named australone B (1) was further isolated from the cortex of Morus australis (Moraceae). The structure of 1 has been elucidated by one- and two-dimension spectra. In human citrated platelet-rich plasma, 1 showed strong inhibition of aggregation induced by adrenaline in a concentration-dependent manner with an IC(50) value of about 33.3 microM. Compound 1 (30 microM) also showed inhibitory effects on superoxide anion formation from rat neutrophils stimulated with formyl-Met-Leu-Phe (fMLP)/cytochalasin B (CB). Morusin (2) inhibited superoxide anion formation from rat neutrophils stimulated with phorbol myristate acetate (PMA) in a concentration-dependent manner with an IC(50) value of 66.9+/-2.5 microM.

Synthesis and Antiplatelet Effects of ω-Aminoalkoxylxanthones

A series of ω‐aminoalkoxylxanthones were synthesized and tested in‐vitro for their ability to inhibit aggregation of rabbit washed platelets and human platelet‐rich plasma (PRP) induced by various inducers. Nine of these compounds showed more potent antiplatelet effects than natural norathyriol tetraacetate on collagen‐induced aggregation. The various ω‐aminoalkoxyl side chains of the synthesized compounds modified the antiplatelet effects. All the compounds tested in human PRP showed significant inhibition of secondary aggregation induced by adrenaline, suggesting that the antiplatelet effects of these compounds is mainly due to an inhibitory effect on thromboxane formation. These compounds at high concentration also cause vasorelaxing action in rat thoracic aorta.

Studies on the Synthesis of Some Xanthonoid Derivatives Possessing Antiplatelet Effects

Abstract— 2,3‐ and 3,4‐Dihydroxyxanthone react with ethyl 2,3‐dibromopropanoate to form the new, substituted 1,4‐benzodioxanes 3 and 4, respectively. The regioisomers 3a and 3b; 4a and 4b were separated by column chromatography and characterized for evaluation of the antiplatelet effects in rabbit washed platelets and human platelet‐rich plasma. The ethoxycarbonyl derivatives 3a (20 μm) and 3b (20 μm) strongly inhibited the aggregation of rabbit washed platelets induced by arachidonic acid and collagen. The compound 4b showed the most potent inhibition of rabbit washed‐platelet aggregation induced by arachidonic acid (IC50 = 8·3 μm). Of the compounds tested in human platelet‐rich plasma, compound 4b exhibited the most potent inhibition of primary and secondary aggregation induced by adrenaline (IC50 = 8·6 μm). We conclude that the antiplatelet effects of these four ethoxycarbonyl derivatives are mainly due to an inhibitory effect on thromboxane formation and interference in the adrenaline‐receptor interaction.

Inhibition of Thromboxane Formation as the Antiplatelet Mechanism of 3,4-Dihydroxyxanthone and Quercetin Pentaacetate

3,4-Dihydroxyxanthone and quercetin pentaacetate were shown to inhibit the aggregation and ATP release of washed rabbit platelets induced by collagen and arachidonic acid, but were not induced by PAF. This inhibition was reversible and in a concentration-dependent manner. The thromboxane B2 formation of washed rabbit platelets, which was caused by arachidonic acid and collagen, was also suppressed by both antiplatelet agents. In human platelet-rich plasma, 3,4-dihydroxyxanthone and quercetin pentaacetate inhibited the secondary, but not the primary aggregation induced by ADP and epinephrine. Both antiplatelet agents also inhibited collagen- and arachidonic acid-induced aggregation in whole blood in a dose-dependent manner. It is concluded that the antiplatelet effects of 3,4-dihydroxyxanthone and quercetin pentaacetate are due to the inhibition of thromboxane formation.

Synthesis, antiplatelet and vasorelaxing effects of monooxygenated flavones and flavonoxypropanolamines

A series of flavones and flavonoxypropanolamines were synthesized and tested in‐vitro for their ability to inhibit aggregation of washed rabbit platelets and human platelet‐rich plasma (PRP), and for vasoconstriction of rat thoracic aorta. The various substituted positions of the hydroxyl group in flavone ring B and the various oxypropanolamine side chains substituted at position C‐2′ of flavone modified the antiplatelet effects. All the compounds tested in human PRP showed significant inhibition of secondary aggregation induced by adrenaline (epinephrine), suggesting that the antiplatelet effect of these compounds is mainly due to an inhibitory effect on thromboxane formation. Compounds 11 and 12 also had potent vasorelaxant effects in rat thoracic aorta. Phenylephrine‐ and high‐K+‐induced 45Ca2+ influx in aorta were both inhibited by the selected compound 11. This result indicates that the inhibitory effect of 11 on the contractile response caused by high‐K+ medium and noradrenaline (norepinephrine) in rat thoracic aorta is mainly due to inhibition of Ca2+ influx through both voltage‐dependent and receptor‐operated Ca2+ channels.