Scopadulciol, an inhibitor of gastric H+, K(+)-ATPase from Scoparia dulcis, and its structure-activity relationships.
A new tetracyclic diterpenoid, scopadulciol [3], together with 6-methoxybenzoxazolinone, glutinol, and acacetin, was isolated from the 70% EtOH extract of Scoparia dulcis collected in Taiwan. Its structure was elucidated to be 6 beta-benzoyl-12-methyl-13-oxo-9(12)a,9(12)b-dihomo-18-podocarpanol on the basis of spectral data. It mildly inhibited hog gastric H+, K(+)-ATPase. Examination of the inhibitory activities of derivatives of scopadulcic acid B [2], including 3, revealed that methylation of the carboxyl group and introduction of an acetyl group or oxime at C-13 or C-18 markedly enhanced the inhibitory activity, while debenzoylation reduced the activity. Among the 30 compounds tested, compound 12, a methyl ester of scopadulcic acid B [2], showed the most potent activity.
Hayashi
T
T
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Asano
S
S
Mizutani
M
M
Takeguchi
N
N
Kojima
T
T
Okamura
K
K
Morita
N
N
D045784:Abietanes; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000818:Animals; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D017506:H(+)-K(+)-Exchanging ATPase; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D010944:Plants; D013329:Structure-Activity Relationship; D013552:Swine
D045784:Abietanes; D004224:Diterpenes; C071755:scopadulciol; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase