Structurally diverse monoterpene indole alkaloids with vasorelaxant activities from the branches of Alstonia scholaris. (May 2023)

• Record Type: Journal Article
• Authors: Zhang, Fuxin; Yang, Kailing; Liu, Huanhuan; Yang, Tao; Zhou, Ruixi; Zhang, Xinxin; Zhan, Guanqun; Guo, Zengjun
• Is Part Of: Phytochemistry. Volume 209(2023)
• Publication Date: 2023-05
• Subjects: Alstonia scholaris (L.) R. Br -- Apocynaceae -- Monoterpene indole alkaloids -- Vasorelaxant activity; Botanical chemistry -- Periodicals; Biochemistry -- Periodicals; Botany -- Periodicals; Chimie végétale -- Périodiques; 572.2
• DOI: 10.1016/j.phytochem.2023.113610
• Languages: English
• ISSNs: 0031-9422

Abstract

Abstract: Seven undescribed monoterpene indole alkaloids alstoscholarinines A‒G, along with nineteen known alkaloids, were isolated from the branches of Alstonia scholaris (L.) R. Br . The isolated alkaloids were classified into ten framework types. The structures of the undescribed alkaloids were elucidated by extensive spectroscopic analysis, ECD calculation, and single-crystal X-ray diffraction analysis. Alstoscholarinine A is an unreported and unusual monoterpene indole alkaloid incorporating three nitrogen atoms, characterized by a compact 6/5/6/6/6/5 hexacyclic system bearing a piperidine ring and a unique oxazolidine ring. Alstoscholarinine B represents the first naturally C-17 nor-isositsirikine-type alkaloid. Plausible biosynthetic pathways of alstoscholarinines A and B were proposed. All isolates were evaluated for their vasorelaxant activities against phenylephrine-induced contraction of rat mesenteric arteries. Among them, seven alkaloids showed significant vasorelaxant activities with EC50 values less than 10 μM. Importantly, the akuammicine-type alkaloids in this study showed much better vasorelaxant activities than other framework type alkaloids, indicating that this type of alkaloid may be a valuable source for the discovery of vasodilators. A preliminary structure-activity relationship for vasorelaxant activities of the isolated akuammicine-type alkaloids is also discussed. Graphical abstract: Seven undescribed alkaloids, including an unprecedented N 3 -type monoterpene indole alkaloid featured by a unique 6/5/6/6/6/5 carbocyclic skeleton, were isolated from the branches of Alstonia scholaris . Some alkaloids showed significant vasorelaxant activities. Image 1 Highlights: Seven undescribed alkaloids, alstoscholarinine A-G, were isolated from A. scholaris. Alstoscholarinine A possessed a unique 6/5/6/6/6/5 carbocyclic skeleton. Alstoscholarinine B was the first naturally C-17 nor-isositsirikine-type alkaloid. Alstoscholarinine G was the first C-20 epi-tubotaiwine-type alkaloid. Seven alkaloids showed significant vasorelaxant activities.