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 Ca²⁺ (1.9 mM) in high K⁺ (80 mM) medium and the phasic and tonic contractions caused by norepinephrine (3 μM). In the rat thoracic aorta, the phenylephrine- and high K⁺-induced ⁴⁵Ca²⁺ 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 Ca²⁺ influx through both voltage-dependent and receptor-operated Ca²⁺ channels. The vasodilating properties of 13 is due to its calcium channel and beta adrenergic blocking effects.