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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Ajmaline / analogs & derivatives*
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Ajmaline / chemistry*
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Ajmaline / pharmacology
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Alstonia / chemistry*
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Animals
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Aorta / drug effects
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Aorta / metabolism
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Calcium / metabolism
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Calcium Channel Blockers / pharmacology
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Calcium Channels / metabolism
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Dose-Response Relationship, Drug
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Drug Evaluation, Preclinical
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Endothelial Cells / drug effects
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Endothelial Cells / metabolism
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In Vitro Techniques
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Magnetic Resonance Spectroscopy
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Male
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Molecular Structure
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Nitric Oxide / metabolism
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Phenylephrine / pharmacology
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Rats
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Rats, Wistar
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Secologanin Tryptamine Alkaloids / chemistry*
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Secologanin Tryptamine Alkaloids / pharmacology*
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Structure-Activity Relationship
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Vasodilation / drug effects
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Vasodilator Agents / chemistry*
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Vasodilator Agents / pharmacology*
Substances
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Calcium Channel Blockers
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Calcium Channels
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Secologanin Tryptamine Alkaloids
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Vasodilator Agents
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alstiphyllanine I
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alstiphyllanine O
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vincamedine
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Ajmaline
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Phenylephrine
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Nitric Oxide
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Calcium