Scopadulcic acid B, a new tetracyclic diterpenoid from Scoparia dulcis L. Its structure, H+, K(+)-adenosine triphosphatase inhibitory activity and pharmacokinetic behaviour in rats.
The structure of scopadulcic acid B (2, SDB), a major ingredient of the Paraguayan herb "Typychá kuratũ" (Scoparia dulcis L.), was elucidated mainly by comparison of its spectral data with that of scopadulcic acid A (1). SDB inhibited both the K(+)-dependent adenosine triphosphatase (ATPase) activity of a hog gastric proton pump (H+, K(+)-ATPase) with a value of 20-30 microM for IC50 and proton transport into gastric vesicles. Pharmacokinetic studies of SDB in rats indicated that plasma SDB concentrations after i.v. injection of the sodium salt of SDB (SDB-Na) were described reasonably well by a two-compartment open model with Michaelis-Menten elimination kinetics. Plasma concentrations after oral administration of SDB-Na or SDB showed a much slower decline than what was expected following the i. v. study. It was suggested that the sustained plasma level of SDB after oral administration of SDB-Na or SDB was accounted for by relatively slow but efficient gastro-intestinal absorption in rats.
Hayashi
T
T
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Okamura
K
K
Kakemi
M
M
Asano
S
S
Mizutani
M
M
Takeguchi
N
N
Kawasaki
M
M
Tezuka
Y
Y
Kikuchi
T
T
Morita
N
N
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D004224:Diterpenes / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D017506:H(+)-K(+)-Exchanging ATPase; D008297:Male; D010239:Paraguay; D010946:Plants, Medicinal / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000187:drug effects / Q000201:enzymology; D013552:Swine; D014961:X-Ray Diffraction
D000998:Antiviral Agents; D004224:Diterpenes; C058658:scopadulcic acid B; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase