Antitussive activity of Stemona alkaloids from Stemona tuberosa

• Published in: Planta medica Vol. 69; no. 10; pp. 914 - 920
• Main Authors: Chung, H.S, Hon, P.M, Lin, G, But, P.P.H, Dong, H
• Format: Journal Article
• Language: English
• Published: Germany 01.10.2003
• Subjects: alkaloids; Alkaloids - administration & dosage; Alkaloids - chemistry; Alkaloids - pharmacology; Alkaloids - therapeutic use; animal models; Animals; antitussive agents; Antitussive Agents - administration & dosage; Antitussive Agents - chemistry; Antitussive Agents - pharmacology; Antitussive Agents - therapeutic use; chemical structure; Citric Acid; Cough - chemically induced; Cough - prevention & control; Dose-Response Relationship, Drug; epi-bisdehydrotuberostemonine; Guinea Pigs; Male; neostenine; neotuberostemonine; phytochemicals; Phytotherapy; plant extracts; Plant Extracts - administration & dosage; Plant Extracts - chemistry; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Plant Roots; spectral analysis; Stemona; Stemona tuberosa; Stemonaceae; stenine; Structure-Activity Relationship; structure-activity relationships; tuberostemonines
• ISSN: 0032-0943; 1439-0221
• DOI: 10.1055/s-2003-45100

Bioactivity-directed fractionation of the crude extract of Stemona tuberosa led to the isolation and characterization of four new stenine-type Stemona alkaloids, namely tuberostemonine J ( 2), tuberostemonine H ( 3), epi-bisdehydrotuberostemonine J ( 4) and neostenine ( 5), together with the known neotuberostemonine ( 1). These five isolated alkaloids were examined for antitussive activity in guinea pig after cough induction by citric acid aerosol stimulation. In this report, we demonstrated, for the first time, that compounds 1 and 5 showed significant antitussive activities. Further study of the structure-activity relationship on these isolated alkaloids and two synthetic analogues revealed that the saturated tricyclic pyrrolo[3,2,1- jk] benzazepine nucleus is the primary key structure contributing to the antitussive activity and all cis configurations at the three ring junctions are the optimal structure for the antitussive activity of stenine-type Stemona alkaloids.