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. 2-Prenyloxyxanthone showed the most potent inhibition of rabbit washed platelet aggregation induced by arachidonic acid (1C50 = 10.2 microM). Of the compounds tested in human PRP, 2-[3 (propylamino)-2-hydroxypropoxy]xanthone (4) hydrochloride salt exhibited the most potent inhibition of platelet aggregation induced by adrenaline (IC50 = 4.4 microM), whereas in evaluation of mouse antithrombotic activity, compound 4 exhibited the most potent protection of mice from thrombotic challenge. Compound 4, 2-[3-(isopropylamino)-2-hydroxypropoxylxanthone hydrochloride salt and 2,5 dihydroxyxanthone suppressed the secondary aggregation induced by adrenaline in human PRP. We conclude that the antiplatelet effects of these compounds are mainly due to an inhibitory effect on thromboxane formation.
School of Pharmacy, Department of Internal Medicine, Kaohsiung Medical College, Taiwan, R.O.C.
C N
CN
Lin
H K
HK
Hsieh
S J
SJ
Liou
H H
HH
Ko
H C
HC
Lin
M I
MI
Chung
F N
FN
Ko
H W
HW
Liu
C M
CM
Teng
D000818:Animals; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013927:Thrombosis / Q000097:blood / Q000517:prevention & control; D014966:Xanthenes / Q000138:chemical synthesis* / Q000494:pharmacology
D005343:Fibrinolytic Agents; D014966:Xanthenes