Vascular L-Type Ca2+ Channel Blocking Activity of Sulfur-Containing Indole Alkaloids from Glycosmis petelotii

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• 作者：Nguyen Manh Cuong ; Pham Ngoc Khanh ; Pham Thu Huyen ; Ho Viet Duc ; Tran Thu Huong ; Vu Thi Ha ; Miriam Durante ; Giampietro Sgaragli ; Fabio Fusi
• 刊名：Journal of Natural Products
• 出版年：2014
• 出版时间：July 25, 2014
• 年：2014
• 卷：77
• 期：7
• 页码：1586-1593
• 全文大小：370K
• ISSN：1520-6025

文摘

In the search for novel natural compounds endowed with potential antihypertensive activity, a new sulfur-containing indole alkaloid, N-demethylglypetelotine (2), and its known analogue glypetelotine (1), were isolated from the leaves of Glycosmis petelotii. Their structures were established on the basis of spectroscopic evidence. The two alkaloids were assessed for vasorelaxing activity on rat aorta rings and for L-type Ba²⁺ current [I_Ba(L)] blocking activity on single myocytes isolated from rat tail artery. Both glypetelotine and N-demethylglypetelotine inhibited phenylephrine-induced contraction with IC₅₀ values of 20 and 50 渭M, respectively. The presence of endothelium did not modify their spasmolytic effect. Neither glypetelotine nor N-demethylglypetelotine affected Ca²⁺ release from the sarcoplasmic reticulum induced by phenylephrine. The spasmolytic effect of glypetelotine increased with membrane depolarization. In the presence of 60 mM K⁺, both compounds inhibited, in a concentration-dependent manner, the contraction induced by cumulative addition of Ca²⁺, this inhibition being inversely related to Ca²⁺ concentration. Glypetelotine and, less efficiently N-demethylglypetelotine, inhibited I_Ba(L), the former compound also affecting I_Ba(L) kinetics. In conclusion, glypetelotine is a novel vasorelaxing agent which antagonizes L-type Ca²⁺ channels.