Positive GABA(A) receptor modulators from Acorus calamus and structural analysis of (+)-dioxosarcoguaiacol by 1D and 2D NMR and molecular modeling.

ABSTRACT: In a two-microelectrode voltage clamp with Xenopus laevis oocytes, a petroleum ether extract of Acorus calamus rhizomes enhanced the GABA-induced chloride current through GABA(A) receptors of the ?????(2S) subtype by 277% ± 9.7% (100 ?g/mL). ?-Asarone (1), (+)-dioxosarcoguaiacol (2), (+)-shyobunone (3), and (+)-preisocalamenediol (4) were subsequently identified as main active principles through HPLC-based activity profiling and targeted isolation. The compounds induced maximum potentiation of the chloride current ranging from 588% ± 126% (EC??: 65.3 ± 21.6 ?M) (2) to 1200% ± 163% (EC(50): 171.5 ± 34.6 ?M) (1), whereas (-)-isoshyobunone (5) and (-)-acorenone (6) exhibited weak GABA(A) modulating properties (5: 164% ± 42.9%; EC??: 109.4 ± 46.6 ?M and 6: 241% ± 23.1%; EC??: 34.0 ± 6.7 ?M). The relative configuration of 2 was established as 4R*8S*10R* by NOESY experiments and conformational analysis.

SUBMITTER: Zaugg J 

PROVIDER: S-EPMC3199944 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature