Antihypertensive and vasorelaxing activities of synthetic xanthone derivatives.
A series of xanthones and xanthonoxypropanolamines have been synthesized. The activity of compounds on cardiovascular system was evaluated. All the compounds tested exhibited effective hypotensive activity in anesthetized rats. An oxypropanolamine side chain substituted at the C-3 position of the xanthone nucleus significantly enhanced the hypotensive activity. In rat thoracic aorta, all the compounds tested significantly depressed the contractions induced by Ca(2+) (1.9mM) in high K+(80mM) medium and the phasic and tonic contractions caused by norepinephrine (3 microM). In the rat thoracic aorta, the phenylephrine- and high K+ -induced 45Ca(2+) influx were both inhibited by a selective xanthone derivative, 13. In addition to the previously reported result of 13, evaluated as beta adrenoceptor blocker, the depressor and bradycardia effects of 9 are independent of the parasympathetic passway. These results suggest that 13 showed inhibitory effects on the contractile response caused by high K+ and norepinephrine in rat thoracic aorta are mainly due to inhibition of Ca(2+) influx through both voltage-dependent and receptor-operated Ca(2+) channels. The vasodilating properties of 13 is due to its calcium channel and beta adrenergic blocking effects.
Wang
Li-Wen
LW
School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan 807, ROC.
Kang
Jaw-Jou
JJ
Chen
Ing-Jun
IJ
Teng
Che-Ming
CM
Lin
Chun-Nan
CN
D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000138:chemical synthesis / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D014966:Xanthenes / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D044004:Xanthones
D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D014665:Vasodilator Agents; D014966:Xanthenes; D044004:Xanthones; C009689:xanthone; D011188:Potassium; D009638:Norepinephrine