Itoigawa M, Takeya K, Furukawa H
Department of Pharmacology, Aichi Medical University, Aichi-ken, Japan.
Arch Int Pharmacodyn Ther. 1990 Nov-Dec;308:95-103.
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.
通过评估一种新型天然物质默里醌 - A及相关化合物在Krebs - Henseleit溶液中对豚鼠乳头肌的正性肌力作用强度，研究了它们的构效关系。在所选的8种化合物中，甲萘醌和白花丹素（芳香甲基 - 对苯醌）引发了强烈的三相性正性肌力反应，如先前报道的默里醌 - A一样。这些活性化合物的效力顺序为：白花丹素（pD2 = 6.40）大于甲萘醌（pD2 = 5.70）大于默里醌 - A（pD2 = 5.27）。芳香甲基 - 对苯醌的去甲基衍生物（咔唑醌、1,4 - 萘醌和2 - 羟基 - 1,4 - 萘醌）以及甲基苯醌（辅酶Q10和2 - 甲基 - 1,4 - 苯醌）未产生任何正性肌力作用。得出结论，芳香甲基 - 对苯醌骨架的存在对于正性肌力反应的产生至关重要。所有情况下该正性肌力作用均为三相性且在缺氧条件下或被2,4 - 二硝基苯酚和双香豆素抑制，这一事实提示了这种正性肌力作用的共同机制。
