Inhibition of mammal Na(+)K(+)-ATPase by diterpenes extracted from the Brazilian brown alga Dictyota cervicornis.
The dolastane diterpenes 4-acetoxy-9,14-dihydroxydolast-1(15),7-diene (1) and 4,7-diacetoxy-14-hydroxydolast-1(15),8-diene (2) were isolated from specimens of the alga Dictyota cervicornis collected from the Rio de Janeiro coast, Brazil. Chemical structures of the diterpenes were assigned by 1D and 2D NMR spectral data for the first time. Both substances inhibited Na(+)K(+)-ATPase preparations from guinea-pig brain or kidney, with the same inhibitory potency towards enzyme isoforms. The maximal inhibition obtained for 1 was 40% at a concentration of 0.5 mm in the incubation mixture, while it reached 80% for compound 2 at this concentration. Ouabain insensitive ATPases were inhibited by 1, but not by 2. Data comparing the inhibitory potency of these compounds with that of ouabain and oleic acid suggest a higher degree of selectivity of 2 towards the Na(+)K(+)-pump. Cardiac glycosides such as ouabain are used classically in the treatment of heart failure, but alterations of Na(+)K(+)-pump activity are also involved in several other diseases. Therefore, the study of compounds interfering with this pump activity is gaining further importance.
Garcia
Diogo Gomes
DG
Departamento de Biologia Celular e Molecular, Instituto de Biologia, Universidade Federal Fluminense, Niterói, RJ, Brazil.
Bianco
Everson Miguel
EM
Santos
Maria da Conceição Batista Dos
Mda C
Pereira
Renato Crespo
RC
Faria
Mauro Velho de Castro
MV
Teixeira
Valeria Laneuville
VL
Burth
Patrícia
P
D000818:Animals; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D006168:Guinea Pigs; D015394:Molecular Structure; D000459:Phaeophyceae / Q000737:chemistry*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism
C542296:4,7-diacetoxy-14-hydroxydolast-1(15),8-diene; C542295:4-acetoxy-9,14-dihydroxydolast-1(15),7-diene; D004224:Diterpenes; D004791:Enzyme Inhibitors; D000254:Sodium-Potassium-Exchanging ATPase