1. Alstiphyllanines I-O, ajmaline type alkaloids from Alstonia macrophylla showing vasorelaxant activity.
- Author
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Arai H, Zaima K, Mitsuta E, Tamamoto H, Saito A, Hirasawa Y, Rahman A, Kusumawati I, Zaini NC, and Morita H
- Subjects
- Ajmaline pharmacology, Animals, Aorta drug effects, Aorta metabolism, Calcium metabolism, Calcium Channel Blockers pharmacology, Calcium Channels metabolism, Dose-Response Relationship, Drug, Drug Evaluation, Preclinical, Endothelial Cells drug effects, Endothelial Cells metabolism, In Vitro Techniques, Magnetic Resonance Spectroscopy, Male, Molecular Structure, Nitric Oxide metabolism, Phenylephrine pharmacology, Rats, Rats, Wistar, Structure-Activity Relationship, Vasodilation drug effects, Ajmaline analogs & derivatives, Ajmaline chemistry, Alstonia chemistry, Secologanin Tryptamine Alkaloids chemistry, Secologanin Tryptamine Alkaloids pharmacology, Vasodilator Agents chemistry, Vasodilator Agents pharmacology
- Abstract
Seven new ajmaline type alkaloids, alstiphyllanines I-O (1-7) were isolated from the leaves of Alstonia macrophylla together with six related alkaloids (8-13). Structures and stereochemistry of 1-7 were fully elucidated and characterized by 2D NMR analysis. A series of alstiphyllanines I-O (1-7) as well as the known ajmaline type alkaloids (8-13) showed that they relaxed phenylephrine (PE)-induced contractions against rat aortic ring. Among them, vincamedine (10) showed potent vasorelaxant activity, which may be mediated through inhibition of Ca(2+) influx through voltage-dependent Ca(2+) channels (VDCs) and/or receptor-operated Ca(2+) channels (ROCs) as well as partially mediated the NO release from endothelial cells. The presence of substituents at both N-1 and C-17 may be important to show vasorelaxation activity., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2012
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