Spasmolytic effects, mode of action, and structure-activity relationships of stilbenoids from Nidema boothii.
A CH(2)Cl(2)-MeOH (1:1) extract prepared from the whole plant of Nidema boothii inhibited spontaneous contractions (IC(50) = 6.26 +/- 2.5 microg/mL) of the guinea-pig ileum. Bioassay-guided fractionation of the active extract led to the isolation of the novel spiro compound 1, which was given the trivial name nidemone, and the new dihydrophenanthrene 3, characterized as 1,5,7-trimethoxy-9,10-dihydrophenanthrene-2,6-diol. In addition, the known stilbenoids aloifol II (2), 1,5,7-trimethoxyphenanthrene-2,6-diol (4), ephemeranthoquinone (5), gigantol (6), ephemeranthol B (7), 2,4-dimethoxyphenanthrene-3,7-diol (8), lusianthridin (9), and batatasin III (10) were obtained. The isolates were characterized structurally by spectroscopic data interpretation. Compounds 2-6, 9, and 10 induced notable concentration-dependent inhibition of the spontaneous contractions of the guinea-pig ileum with IC(50) values that ranged between 0.14 and 2.36 microM. Bibenzyl analogues 23-35 were synthesized and tested pharmacologically. The results indicated that for maximum spasmolytic activity the bibenzyls should have oxygenated substituents on both aromatic rings; on the other hand, methylation of free hydroxyl groups as well as the increment of oxygenated groups in relation to compounds 6 and 10 decreased the smooth muscle relaxant activity. It was also demonstrated that bibenzyls 6 and 10 might exert their spasmolytic action not only by a nitrergic mechanism but also by inhibiting CaM-mediated processes.
Hernández-Romero
Yanet
Y
Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Coyoacán, D.F 04510, México.
Rojas
Juana-Isela
JI
Castillo
Rafael
R
Rojas
Alejandra
A
Mata
Rachel
R
D000818:Animals; D001632:Bibenzyls; D001921:Brain / Q000187:drug effects; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D006139:Guaiacol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum; D020128:Inhibitory Concentration 50; D008800:Mexico; D008954:Models, Biological; D008968:Molecular Conformation; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects*; D029595:Orchidaceae / Q000737:chemistry*; D010276:Parasympatholytics / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects / Q000378:metabolism; D010946:Plants, Medicinal / Q000737:chemistry*; D013141:Spiro Compounds / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D013267:Stilbenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D001632:Bibenzyls; D005419:Flavonoids; D010276:Parasympatholytics; D013141:Spiro Compounds; D013267:Stilbenes; C483640:nidemone; C478099:gigantol; D006139:Guaiacol; D010727:Phosphoric Diester Hydrolases