Structure-activity relationship studies on chalcone derivatives: potent inhibition of platelet aggregation.
In an effort to develop potent antiplatelet agents with anti-inflammatory action, a novel series of anti-inflammatory chalcones was screened to evaluate their antiplatelet effects. Structure-activity relationships and mode of action were investigated and characterized. The antiplatelet effects of the chalcones on washed rabbit platelets and human platelet-rich plasma were evaluated. Arachidonic acid-induced platelet aggregation was potently inhibited by almost all the chalcone derivatives. Collagen-induced platelet aggregation was potently inhibited by all the chalcone derivatives at 300 microM, except for compound 4 at 100 microM. Compounds 6, 7 and 9 significantly inhibited the aggregation of washed rabbit platelets induced by platelet-activating factor at 300 microM. Of the compounds tested in human platelet-rich plasma, compounds 2, 8 and 9 showed significant inhibition of secondary aggregation induced by adrenaline. It is concluded that the antiplatelet effect of 2, 8 and 9 is mainly owing to an inhibitory effect on thromboxane formation. The inhibitory effect of 6, 7 and 9 on platelet aggregation induced by platelet-activating factor could be owing to a calcium antagonizing effect or inhibition of intracellular calcium mobilization.
Ko
Horng-Huey
HH
Faculty of Fragrance and Cosmetics, Kaohsiung Medical University, Kaohsiung, Taiwan.
Hsieh
Hsin-Kaw
HK
Liu
Cheng-Tsung
CT
Lin
Hsien-Chen
HC
Teng
Che-Ming
CM
Lin
Chun-Nan
CN
D000818:Animals; D016718:Arachidonic Acid; D047188:Chalcones / Q000138:chemical synthesis* / Q000494:pharmacology*; D003094:Collagen; D004837:Epinephrine; D006801:Humans; D015394:Molecular Structure; D010972:Platelet Activating Factor; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D011817:Rabbits; D013329:Structure-Activity Relationship; D013917:Thrombin
D047188:Chalcones; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D003094:Collagen; D013917:Thrombin; D004837:Epinephrine