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.
Subject(s)
Ajmaline/analogs & derivatives , Ajmaline/chemistry , Alstonia/chemistry , Secologanin Tryptamine Alkaloids/chemistry , Secologanin Tryptamine Alkaloids/pharmacology , Vasodilator Agents/chemistry , Vasodilator Agents/pharmacology , 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 effectsABSTRACT
Five bisbenzyl isoquinolines (1-5), three benzyl isoquinolines (6-8), four isoquinoline alkaloids (9-12), and two unclassified compounds (13 and 14) from Popowia perakensis and Phaeanthus crassipetalus were evaluated for their vasorelaxant effect on rat aortic arteries. In aortic rings pre-contracted with phenylephrine (PE, 0.3 µM), some of the bisbenzyl isoquinoline alkaloids, benzyl isoquinoline alkaloids, and isoquinoline alkaloids showed clearly vasorelaxant effects at 30 µM. The action of (-)-limacine (4) was deduced to be mediated through the increased release of NO from endothelial cells, and that of pecrassipine A (7) and backebergine (12) partly mediated by NO release. Further, the action of pecrassipine A (7) and backebergine (12) may be attributed to their inhibition of the voltage-dependent Ca(2+) channel and receptor-operated Ca(2+) channel.
Subject(s)
Alkaloids/pharmacology , Annonaceae/chemistry , Aorta/drug effects , Arteries/drug effects , Plants, Medicinal/chemistry , Vasodilator Agents/pharmacology , Alkaloids/chemistry , Animals , Endothelial Cells/drug effects , Endothelial Cells/metabolism , In Vitro Techniques , Isoquinolines/chemistry , Isoquinolines/pharmacology , Male , Nitric Oxide/metabolism , Phenylephrine/chemistry , Phenylephrine/pharmacology , Rats , Rats, Wistar , Vasodilator Agents/chemistryABSTRACT
Vasorelaxant effects of a series of bis(bibenzyls) from liverworts such as Marchantia polymorpha and Marchantia paleacea on rat aorta demonstrated that they relaxed phenylephrine (PE)-induced contractions, which may be mediated through the increased release of NO from endothelial cells as well as opening of K(+) channels, and inhibition of Ca(2+) influx through voltage-dependent Ca(2+) channels (VDCs) and/or receptor-operated Ca(2+) channels (ROCs). Structure-activity relationship based on their structures was discussed. The presence of two aromatic rings which can be connected through two atoms bridge spacer may play an important role for vasorelaxant effect.
