Antitussive activity of Stemona alkaloids from Stemona tuberosa.
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.
Chung
Hoi-Sing
HS
Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR.
Hon
Po-Ming
PM
Lin
Ge
G
But
Paul Pui-Hay
PP
Dong
Hui
H
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
D000470:Alkaloids; D000996:Antitussive Agents; D010936:Plant Extracts; D019343:Citric Acid