Studies on the synthesis of some xanthonoid derivatives possessing antiplatelet effects.
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 microM) and 3b (20 microM) 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 microM). 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 microM). 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.
Lin
C N
CN
Natural Products Research Centre, Kaohsiung Medical College, Taiwan, R.O.C.
Fang
S C
SC
Lin
H C
HC
Ko
F N
FN
Shieh
B J
BJ
Liu
H W
HW
Teng
C M
CM
D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D011817:Rabbits; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D014966:Xanthenes / Q000138:chemical synthesis* / Q000494:pharmacology*
D000959:Antihypertensive Agents; D010975:Platelet Aggregation Inhibitors; D014966:Xanthenes; D004837:Epinephrine