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.
Chung
M I
MI
School of Pharmacy, Kaohsiung Medical University, Taiwan, Republic of China. meinch@cc.kmu.edu.tw
Han
F W
FW
Lin
H C
HC
Liou
S S
SS
Huang
P L
PL
Ko
H H
HH
Chang
Y L
YL
Kang
J J
JJ
Teng
C M
CM
Lin
C N
CN
D000818:Animals; D002118:Calcium / Q000378:metabolism; D005260:Female; D005419:Flavonoids / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011412:Propanolamines / Q000138:chemical synthesis* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000494:pharmacology
D005419:Flavonoids; D010975:Platelet Aggregation Inhibitors; D011412:Propanolamines; D014665:Vasodilator Agents; D002118:Calcium