title: Antitussive activity of Stemona alkaloids from Stemona tuberosa.
abstract: 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.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR.
authors.forename: Hoi-Sing
authors.initials: HS
authors.lastname: Chung
authors.forename: Po-Ming
authors.initials: PM
authors.lastname: Hon
authors.forename: Ge
authors.initials: G
authors.lastname: Lin
authors.forename: Paul Pui-Hay
authors.initials: PP
authors.lastname: But
authors.forename: Hui
authors.initials: H
authors.lastname: Dong
mesh_terms: D000470:Alkaloids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000996:Antitussive Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D019343:Citric Acid; D003371:Cough / Q000139:chemically induced / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008297:Male; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D018517:Plant Roots; D041901:Stemonaceae; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D000996:Antitussive Agents; D010936:Plant Extracts; D019343:Citric Acid