title: Structure-activity relationship for the inotropic effect of aromatic methyl-p-quinones.
abstract: The structure-activity relationship of a novel natural substance murrayaquinone-A and related compounds, was studied by evaluating their positive inotropic potencies on guinea-pig papillary muscle in Krebs-Henseleit solution. Among the selected eight compounds, menadione and plumbagin (aromatic methyl-p-quinone) induced a potent triphasic inotropic response, as reported previously for murrayaquinone-A. The order of potency of these active compounds was: plumbagin (pD2 = 6.40) greater menadione (pD2 = 5.70) greater than murrayaquinone-A (pD2 = 5.27). Demethyl derivatives of aromatic methyl-p-quinones (carbazolequinone, 1,4-naphthoquinone and 2-hydroxy-1,4-naphthoquinone) and methyl-benzoquinones (co-enzyme Q10 and 2-methyl-1,4-benzoquinone) did not produce any positive inotropic effect. It is concluded that the presence of the aromatic methyl-p-quinone skeleton is essential for the development of an inotropic response. A common mechanism for this positive inotropic effect is suggested by the fact that in all cases it was triphasic in nature and inhibited in anoxic conditions or by 2,4-dinitrophenol and dicumarol.
authors.affiliation: Department of Pharmacology, Aichi Medical University, Aichi-ken, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Itoigawa
authors.forename: K
authors.initials: K
authors.lastname: Takeya
authors.forename: H
authors.initials: H
authors.lastname: Furukawa
mesh_terms: D000470:Alkaloids; D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D016227:Benzoquinones; D002227:Carbazoles; C062196:murrayaquinone A