Alstiphyllanines I-O, ajmaline type alkaloids from Alstonia macrophylla showing vasorelaxant activity

作者：Arai Hiroko; Zaima Kazumasa; Mitsuta Erika; Tamamoto Haruka; Saito Aiko; Hirasawa Yusuke; Rahman Abdul; Kusumawati Idha; Zaini Noor Cholies; Morita Hiroshi^*

来源：Bioorganic & Medicinal Chemistry, 2012, 20(11): 3454-3459.

DOI：10.1016/j.bmc.2012.04.013

• Indole alkaloids
• Alstonia macrophylla
• Alstiphyllanines I-O
• Ajmaline type alkaloids
• Vasorelaxant activity
• Nitric oxide
• VDCs
• ROCs
• SAR

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 Ca2+ influx through voltage-dependent Ca2+ channels (VDCs) and/or receptor-operated Ca2+ 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.

• 出版日期2012-6-1