Inhibition of mammal Na⁺K⁺‐ATPase by diterpenes extracted from the Brazilian brown alga Dictyota cervicornis

Abstract

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.

What are and where are the bioactive terpenoids metabolites from Dictyotaceae (Phaeophyceae)

“…This last activity was also shown by Canistrocarpus dolastanes (Garcia et al, 2009). Antiviral activity, in particular that against HIV and HSV, was exhibited by several Meroditerpenes from Stypopodium (Soares et al, 2007), by dichotomane (Pereira et al, 2004), and by dolabellane (Barbosa et al, 2004a).…”

Chemical defenses of the tropical marine seaweed Canistrocarpus cervicornis against herbivory by sea urchin

“…From the most consumed deterrent extract (DCE) against L. variegatus was isolated the major diterpene compound identified as (4R,7R,14S)-4α,7α-Diacetoxy-14-hydroxydolast-1(15),8-diene (GARCIA et al, 2009).…”

“…Next, the DCE (dichloromethane crude extract) was assayed by 1 H NMR and the spectra shifts showed a dolastane diterpene as the major compound: 4.91 (bs, 1H), 4.86 (bs, 1H), 0.88 (s, 3H), 2.79 (septet, 1H, J = 6.9), 0.94 (d, 3H, J = 6.9), 0.91 (d, 3H, J = 6.9), 1.47 (s, 3H), 2.15 (s, 3H), 2.02 (s, 3H), 3.71 (bs, 1H) (GONZÁLEZ et al, 1983;SUN et al, 1981). The complete structural elucidation of this diterpene was obtained by 1 H NMR and 13 C-APT NMR assays, the spectral data having been previously reported (GARCIA et al, 2009).…”

“…The complete structural elucidation of this diterpene was obtained by 1 H NMR and 13 C-APT NMR assays, the spectral data having been previously reported (GARCIA et al, 2009). …”

Seaweeds as Source of New Bioactive Prototypes

“…Both diterpenes have been shown to inhibit the activity of organ crude homogenates and purified Na+K+-ATPase of the kidney and brain. Compound 10 showed the best results [47]. The other two dolastane diterpenes were isolated from brown seaweed C. cervicornis and evaluated their cytotoxicity in Vero cells and antiviral activity (HSV-1).…”